PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 32713032-0 2021 Impairment of endoxifen formation in tamoxifen-treated premenopausal breast cancer patients carrying reduced-function CYP2D6 alleles. Tamoxifen 37-46 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 118-124 33047329-9 2021 This popPK model can be used as a tool to predict ENDO levels or AAS according to patient"s CYP2D6 phenotype for TAM dose adaptation. Tamoxifen 113-116 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 92-98 33757925-15 2021 On the one hand because all phytoestrogens are contraindicated and on the other hand, in patients using tamoxifen, because the molecules, that interact with CYP2D6, are to be formally avoided because of potential interaction with this anti-estrogen treatment. Tamoxifen 104-113 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 157-163 32713032-1 2021 AIMS: Tamoxifen is bioactivated to endoxifen by polymorphic CYP2D6-dependent metabolism. Tamoxifen 6-15 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 60-66 33515076-9 2021 CONCLUSION: This review revealed more systematic pharmacogenomics of genes involved in the metabolism and transport besides CYP2D6, are required to optimize the genotyping strategies and guide the personalized tamoxifen therapy in Asian populations. Tamoxifen 210-219 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 124-130 33673305-4 2021 The association between genetically compromised CYP2D6 activity and low endoxifen plasma concentrations is generally accepted, and it was shown that tamoxifen dose increments in compromised patients resulted in higher endoxifen concentrations. Tamoxifen 149-158 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 48-54 33673305-7 2021 This paper describes the latest developments on CYP2D6 genotyping in relation to endoxifen plasma concentrations and tamoxifen-related clinical outcome. Tamoxifen 117-126 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 48-54 33320718-5 2021 EXPERT OPINION: We believe that at least the main candidate factors, i.e. CYP2D6 polymorphism, CYP2D6 inhibition, endoxifen serum levels may become important predictors of clinical relevance for tamoxifen treatment personalization in the future. Tamoxifen 195-204 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 74-80 33320718-5 2021 EXPERT OPINION: We believe that at least the main candidate factors, i.e. CYP2D6 polymorphism, CYP2D6 inhibition, endoxifen serum levels may become important predictors of clinical relevance for tamoxifen treatment personalization in the future. Tamoxifen 195-204 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 95-101 33673305-0 2021 Clinical CYP2D6 Genotyping to Personalize Adjuvant Tamoxifen Treatment in ER-Positive Breast Cancer Patients: Current Status of a Controversy. Tamoxifen 51-60 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 9-15 33673305-2 2021 The conversion of the prodrug tamoxifen into the most active metabolite endoxifen is mainly catalyzed by the enzyme cytochrome P450 2D6 (CYP2D6). Tamoxifen 30-39 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 116-135 33673305-2 2021 The conversion of the prodrug tamoxifen into the most active metabolite endoxifen is mainly catalyzed by the enzyme cytochrome P450 2D6 (CYP2D6). Tamoxifen 30-39 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 137-143 32501544-4 2021 Other associations such as CYP2D6 status in determining the efficacy of tamoxifen are more controversial because of contradictory evidence from different sources, which has led to variability in the implementation of testing. Tamoxifen 72-81 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 27-33 31916635-4 2020 Here in we report the design and synthesis of 10 novel compounds bearing a modified tamoxifen skeleton, ring C is substituted with different ester groups to bypass the CYP2D6 enzyme metabolism and employ esterase enzymes for activation. Tamoxifen 84-93 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 168-174 33369460-0 2020 The Role of CYP2D6 Polymorphisms in Determining Response to Tamoxifen in Metastatic Breast Cancer Patients: Review and Egyptian Experience. Tamoxifen 60-69 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 12-18 33369460-3 2020 The aim of this study was to assess the prognostic and predictive value(s) of CYP2D6 polymorphisms in Tamoxifen responders and non-responders. Tamoxifen 102-111 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 78-84 33369460-9 2020 CONCLUSION: CYP2D6 polymorphisms can significantly predict response to Tamoxifen treatment, and also associates with poor overall survival rates in MBC patients. Tamoxifen 71-80 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 12-18 33161337-0 2020 Simplified phenotyping of CYP2D6 for tamoxifen treatment using the N-desmethyl-tamoxifen/ endoxifen ratio. Tamoxifen 37-46 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 26-32 33191836-0 2022 Reduction in Tamoxifen Metabolites Endoxifen and N-desmethyltamoxifen With Chronic Administration of Low Dose Cannabidiol: A CYP3A4 and CYP2D6 Drug Interaction. Tamoxifen 13-22 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 136-142 31916635-0 2020 Synthesis of novel flexible tamoxifen analogues to overcome CYP2D6 polymorphism and their biological evaluation on MCF-7 cell line. Tamoxifen 28-37 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 60-66 31916635-2 2020 TAM is activated by endogenous CYP450 enzymes to the more biologically active metabolites 4-hydroxytamoxifen and endoxifen mainly via CYP2D6 and CYP3A4/5. Tamoxifen 0-3 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 134-140 32270286-1 2020 PURPOSE: To review recent pharmacogenomics studies on breast cancer patients undergoing tamoxifen therapy, highlighting how our knowledge on cytochrome P450 2D6 (CYP2D6) can help to guide the development of adjuvant therapies for these patients. Tamoxifen 88-97 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 141-160 31916635-3 2020 CYP2D6 has been investigated for polymorphism; there is a large interindividual variation in the enzyme activity, this drastically effects clinical outcomes of tamoxifen treatment. Tamoxifen 160-169 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 32270286-1 2020 PURPOSE: To review recent pharmacogenomics studies on breast cancer patients undergoing tamoxifen therapy, highlighting how our knowledge on cytochrome P450 2D6 (CYP2D6) can help to guide the development of adjuvant therapies for these patients. Tamoxifen 88-97 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 162-168 32270286-4 2020 RESULTS: With CYP2D6 being the primary enzyme for tamoxifen metabolism, single-nucleotide polymorphisms (SNPs) in this gene were one of the determinants in the rate of tamoxifen metabolism, thereby potentially having an effect on the efficacy of tamoxifen-based therapies. Tamoxifen 50-59 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 14-20 32270286-4 2020 RESULTS: With CYP2D6 being the primary enzyme for tamoxifen metabolism, single-nucleotide polymorphisms (SNPs) in this gene were one of the determinants in the rate of tamoxifen metabolism, thereby potentially having an effect on the efficacy of tamoxifen-based therapies. Tamoxifen 168-177 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 14-20 32270286-4 2020 RESULTS: With CYP2D6 being the primary enzyme for tamoxifen metabolism, single-nucleotide polymorphisms (SNPs) in this gene were one of the determinants in the rate of tamoxifen metabolism, thereby potentially having an effect on the efficacy of tamoxifen-based therapies. Tamoxifen 168-177 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 14-20 32270286-5 2020 Our review indicates the potential effectiveness of targeting these SNPs, including those for the CYP2D6*10 allele (c. 100C > T), in modifying the level of tamoxifen metabolism. Tamoxifen 156-165 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 98-104 32270286-9 2020 Research efforts should be directed towards the exploration of further SNPs of CYP2D6 that affect tamoxifen metabolism, as well as epigenetic changes in CYP2D6, enabling the design of precision medicine and confirming clinical validity in the use of pharmacogenomics for tamoxifen. Tamoxifen 98-107 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 79-85 31758654-8 2020 The genetic component (rGC) of the CYP2D6-mediated conversion of tamoxifen into endoxifen, estimated using the repeated drug administration procedure across the three phases, was 0.87, pointing to an important component of genetic variability. Tamoxifen 65-74 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 35-41 31877313-0 2020 Impact of CYP2D6 polymorphisms on tamoxifen treatment in patients with retroperitoneal fibrosis: A first step towards tailored therapy? Tamoxifen 34-43 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 10-16 32273802-1 2020 Consumption of Cytochrome P450 2D6 (CYP2D6) inhibiting drugs along with tamoxifen treatment results in decrease in plasma concentration of endoxifen, the major active tamoxifen metabolite. Tamoxifen 72-81 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 15-34 32273802-1 2020 Consumption of Cytochrome P450 2D6 (CYP2D6) inhibiting drugs along with tamoxifen treatment results in decrease in plasma concentration of endoxifen, the major active tamoxifen metabolite. Tamoxifen 72-81 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 36-42 32273802-1 2020 Consumption of Cytochrome P450 2D6 (CYP2D6) inhibiting drugs along with tamoxifen treatment results in decrease in plasma concentration of endoxifen, the major active tamoxifen metabolite. Tamoxifen 167-176 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 15-34 32273802-1 2020 Consumption of Cytochrome P450 2D6 (CYP2D6) inhibiting drugs along with tamoxifen treatment results in decrease in plasma concentration of endoxifen, the major active tamoxifen metabolite. Tamoxifen 167-176 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 36-42 32273802-2 2020 Simultaneous use of CYP2D6 inhibitors, such as selective serotonin reuptake inhibitors (SSIs), as well as lesser tamoxifen adherence may negatively impact tamoxifen efficacy in patients with breast cancer. Tamoxifen 155-164 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 20-26 31877313-1 2020 OBJECTIVE: To investigate the influence of CYP2D6 polymorphisms on outcomes and health-related quality of life (HRQoL) of patients with retroperitoneal fibrosis (RPF) receiving tamoxifen (TMX). Tamoxifen 177-186 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 43-49 31877313-3 2020 Conversion of tamoxifen to more potent endoxifen is dependent on enzyme activity of CYP2D6. Tamoxifen 14-23 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 84-90 31877313-4 2020 MATERIALS AND METHODS: CYP2D6 genotyping and phenotype prediction of all patients treated with tamoxifen between 02/2007-01/2018 was assessed using multiplex PCR. Tamoxifen 95-104 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 23-29 32047265-11 2021 Furthermore, our data-driven enrichment analysis showed that CYP2D6 is significantly involved in drug metabolism of codeine, tamoxifen, and citalopram. Tamoxifen 125-134 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 61-67 31821071-0 2020 CYP2D6 Genotype-Guided Tamoxifen Dosing in Hormone Receptor-Positive Metastatic Breast Cancer (TARGET-1): A Randomized, Open-Label, Phase II Study. Tamoxifen 23-32 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 31821071-1 2020 PURPOSE: In patients taking tamoxifen, the CYP2D6 genotype causes different exposure of active metabolite endoxifen. Tamoxifen 28-37 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 43-49 31821071-2 2020 The objective of this randomized, open-label, multicenter, phase II study was to prospectively evaluate whether CYP2D6 genotype-guided tamoxifen dosing in patients with hormone receptor-positive metastatic breast cancer could have an impact on the clinical outcome. Tamoxifen 135-144 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 112-118 31800347-0 2020 CYP2D6 Genotype Predicts Tamoxifen Discontinuation and Prognosis in Patients With Breast Cancer. Tamoxifen 25-34 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 31800347-5 2020 RESULTS: The 6-month discontinuation rates of tamoxifen among poor, intermediate, normal, and ultrarapid CYP2D6 metabolizers were 7.1%, 7.6%, 6.7%, and 18.8%, respectively. Tamoxifen 46-55 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 105-111 31800347-7 2020 CONCLUSION: Both poor and ultrarapid CYP2D6 metabolizers of tamoxifen have a worse prognosis for breast cancer compared with normal metabolizers after receiving a standard dose of tamoxifen. Tamoxifen 60-69 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 37-43 31800347-7 2020 CONCLUSION: Both poor and ultrarapid CYP2D6 metabolizers of tamoxifen have a worse prognosis for breast cancer compared with normal metabolizers after receiving a standard dose of tamoxifen. Tamoxifen 180-189 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 37-43 31852530-1 2019 BACKGROUND: Tamoxifen is considered a prodrug of its active metabolite endoxifen, which is dependent on the CYP2D6 and CYP3A enzymes. Tamoxifen 12-21 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 108-114 32080081-5 2020 Polymorphisms in genes involved in the metabolism of tamoxifen (ie, CYP3A4, CYP2D6) may influence responses to tamoxifen. Tamoxifen 53-62 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 76-82 32080081-5 2020 Polymorphisms in genes involved in the metabolism of tamoxifen (ie, CYP3A4, CYP2D6) may influence responses to tamoxifen. Tamoxifen 111-120 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 76-82 31559573-1 2020 BACKGROUND: A CYP2D6 gene polymorphism is related to the effect of tamoxifen treatment in patient with estrogen-receptor positive (ER) positive breast cancer and CYP2D6*10 T/T can lead to a poor prognosis in Asian patients. Tamoxifen 67-76 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 14-20 31559573-1 2020 BACKGROUND: A CYP2D6 gene polymorphism is related to the effect of tamoxifen treatment in patient with estrogen-receptor positive (ER) positive breast cancer and CYP2D6*10 T/T can lead to a poor prognosis in Asian patients. Tamoxifen 67-76 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 162-168 34007593-1 2019 The objective is to report a case of recurrent breast cancer in a poor CYP2D6 metabolizer male patient on tamoxifen, and how pharmacogenomic (PGx) testing can play an important role in selecting appropriate adjuvant endocrine therapy. Tamoxifen 106-115 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 71-77 34007593-4 2019 PGx testing ordered at the time of recurrence revealed patient is a poor metabolizer of CYP2D6, which may decrease the efficacy of tamoxifen. Tamoxifen 131-140 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 88-94 31195002-2 2019 Cytochrome P450 (CYP) 2D6 is crucial in the oxidation of tamoxifen to generate active metabolites, 4-hydroxytamoxifen and endoxifen. Tamoxifen 57-66 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-25 31547390-0 2019 CYP2D6 Genotype Predicts Plasma Concentrations of Tamoxifen Metabolites in Ethiopian Breast Cancer Patients. Tamoxifen 50-59 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 30734152-1 2019 BACKGROUND: An association between CYP2D6 polymorphisms and tamoxifen (TAM) efficacy has not been confirmed, partly due to unreliable prediction of active metabolite exposure solely by CYP2D6 activity. Tamoxifen 60-69 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 35-41 30734152-1 2019 BACKGROUND: An association between CYP2D6 polymorphisms and tamoxifen (TAM) efficacy has not been confirmed, partly due to unreliable prediction of active metabolite exposure solely by CYP2D6 activity. Tamoxifen 71-74 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 35-41 30734152-10 2019 The CYP2D6 genotype was the major determinant for TAM activity (p < 0.01). Tamoxifen 50-53 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 4-10 30786012-5 2019 Comparison of endoxifen levels showed that the CYP2D6 phenotype classification could be improved by grouping intermediate metabolizer (IM)/IM and IM/poor metabolizer diplotype into IM phenotype for future use in tamoxifen therapy optimization. Tamoxifen 212-221 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 47-53 30786012-6 2019 Finally, the multivariable regression analysis showed that formation of tamoxifen metabolites was independently impacted by CYP2D6 diplotype and CYP3A4*22, CYP2C19*2, and CYP2B6*6 genetic polymorphisms. Tamoxifen 72-81 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 124-130 28520357-0 2012 Tamoxifen Therapy and CYP2D6 Genotype Tamoxifen is a selective estrogen receptor modulator (SERM) which is used in the treatment and prevention of breast cancer (1). Tamoxifen 38-47 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 22-28 31344832-0 2019 Non-CYP2D6 Variants Selected by a GWAS Improve the Prediction of Impaired Tamoxifen Metabolism in Patients with Breast Cancer. Tamoxifen 74-83 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 4-10 31344832-10 2019 In conclusion, the four novel SNPs, tested alone or in combination with the CYP2D6 genotype, improved the prediction of impaired tamoxifen-to-endoxifen metabolism, potentially allowing for treatment optimization. Tamoxifen 129-138 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 76-82 31284530-2 2019 CYP2D6 is a key metabolizing enzyme that is involved in the conversion of tamoxifen to its active drug metabolites. Tamoxifen 74-83 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 31284530-3 2019 CYP2D6 has several alleles that metabolize tamoxifen and other drugs at different rates that can alter therapeutic impact, a characteristic that renders it one of the most studied enzymes in the field of pharmacogenetics. Tamoxifen 43-52 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 31284530-5 2019 Therefore, we aim to investigate the impact of CYP2D6 genotyping of the tamoxifen metabolizing enzymes in the clinical management of breast cancer patients. Tamoxifen 72-81 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 47-53 31008668-2 2019 Tamoxifen has a complex metabolism, being mainly metabolized by CYP2D6 into its 30-100 times more potent metabolite, endoxifen. Tamoxifen 0-9 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 64-70 31178724-0 2019 Clinical Trial: CYP2D6 Related Dose Escalation of Tamoxifen in Breast Cancer Patients With Iranian Ethnic Background Resulted in Increased Concentrations of Tamoxifen and Its Metabolites. Tamoxifen 50-59 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 16-22 31178724-0 2019 Clinical Trial: CYP2D6 Related Dose Escalation of Tamoxifen in Breast Cancer Patients With Iranian Ethnic Background Resulted in Increased Concentrations of Tamoxifen and Its Metabolites. Tamoxifen 157-166 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 16-22 31178724-1 2019 Introduction: The polymorphic enzyme cytochrome P450 2D6 (CYP2D6) catalyzes a major step in the bioactivation of tamoxifen. Tamoxifen 113-122 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 37-56 31178724-1 2019 Introduction: The polymorphic enzyme cytochrome P450 2D6 (CYP2D6) catalyzes a major step in the bioactivation of tamoxifen. Tamoxifen 113-122 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 58-64 31178724-3 2019 The aim of this study was to investigate the relationship between the plasma levels of tamoxifen and its metabolites and different CYP2D6 genotypes under standard (20 mg/day) and dose-adjusted therapy (Registration ID in Iranian Registry of Clinical Trials: IRCT2015082323734N1). Tamoxifen 87-96 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 131-137 31178724-10 2019 Conclusion: For the first time, we show the feasibility of dose escalation of tamoxifen in breast cancer patients with compromised CYP2D6 activity and Iranian ethnic background to increase the plasma concentrations of (Z)-endoxifen. Tamoxifen 78-87 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 131-137 28520357-1 2012 The CYP2D6 enzyme metabolizes a quarter of all prescribed drugs, and is one of the main enzymes responsible for converting tamoxifen into its major active metabolite, endofixen. Tamoxifen 123-132 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 4-10 28520357-6 2012 In contrast, the Dutch Pharmacogenetics Working Group has made recommendations for tamoxifen therapy based on CYP2D6 genotypes. Tamoxifen 83-92 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 110-116 30658716-11 2019 VAE preparations did not cause inhibition of CYP3A4/5 and CYP2D6 catalyzed tamoxifen metabolism. Tamoxifen 75-84 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 58-64 30792473-0 2019 Dynamic Effects of CYP2D6 Genetic Variants in a Set of Poor Metaboliser Patients with Infiltrating Ductal Cancer Under Treatment with Tamoxifen. Tamoxifen 134-143 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 19-25 30792473-3 2019 Tamoxifen is catalysed by cytochrome P450 2D6 (CYP2D6), and inter-individual variations in the enzyme due to single nucleotide polymorphisms (SNPs) could alter enzyme activity. Tamoxifen 0-9 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 26-45 30792473-3 2019 Tamoxifen is catalysed by cytochrome P450 2D6 (CYP2D6), and inter-individual variations in the enzyme due to single nucleotide polymorphisms (SNPs) could alter enzyme activity. Tamoxifen 0-9 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 47-53 30792473-7 2019 Although we found no significant structural change in the protein, its dynamics differ significantly from those of CYP2D6*1, the effect of such differential dynamics resulting in an inefficient enzyme with serious implications for tamoxifen-treated patients, increasing the risk of disease relapse and ineffective treatment. Tamoxifen 231-240 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 115-121 30411242-3 2019 Since CYP2D6 genetic variants have been reported to play an important role in survival outcomes after treatment with tamoxifen, this study sought to summarize and critically appraise the available scientific evidence on this topic. Tamoxifen 117-126 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 6-12 30411242-4 2019 METHODS: A systematic literature review was conducted to identify studies investigating associations between CYP2D6 genetic variation and survival outcomes after tamoxifen treatment. Tamoxifen 162-171 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 109-115 30411242-5 2019 Critical appraisal of the retrieved scientific evidence was performed, and recommendations were developed for CYP2D6 genetic testing in the context of tamoxifen therapy. Tamoxifen 151-160 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 110-116 30411242-6 2019 RESULTS: Although conflicting literature exists, the majority of the current evidence points toward CYP2D6 genetic variation affecting survival outcomes after tamoxifen treatment. Tamoxifen 159-168 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 100-106 30411242-9 2019 Based on this information, it is recommended that alternatives to standard tamoxifen treatments may be considered in CYP2D6 poor or intermediate metabolizers. Tamoxifen 75-84 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 117-123 30357449-0 2019 Effects of CYP2D6*10 polymorphism on tamoxifen pharmacokinetics in patients with breast cancer in Asia: a meta-analysis. Tamoxifen 37-46 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 11-17 30542984-0 2019 CYP2D6-inhibiting medication use and inherited CYP2D6 variation in relation to adverse breast cancer outcomes after tamoxifen therapy. Tamoxifen 116-125 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 30542984-0 2019 CYP2D6-inhibiting medication use and inherited CYP2D6 variation in relation to adverse breast cancer outcomes after tamoxifen therapy. Tamoxifen 116-125 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 47-53 30357449-12 2019 CONCLUSIONS: CYP2D6*10 polymorphisms influence the pharmacokinetics of tamoxifen in patients with breast cancer in Asia. Tamoxifen 71-80 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 13-19 30542984-2 2019 Tamoxifen efficacy is thought to be attributable to its active metabolite, which is formed through a reaction catalyzed by the P450 enzyme, CYP2D6. Tamoxifen 0-9 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 140-146 30542984-3 2019 Inhibition of tamoxifen metabolism as a result of germline genetic variation and/or use of CYP2D6-inhibiting medications ("inhibitors") is hypothesized to increase the risk of adverse BC outcomes among women taking tamoxifen. Tamoxifen 14-23 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 91-97 30542984-3 2019 Inhibition of tamoxifen metabolism as a result of germline genetic variation and/or use of CYP2D6-inhibiting medications ("inhibitors") is hypothesized to increase the risk of adverse BC outcomes among women taking tamoxifen. Tamoxifen 215-224 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 91-97 30843495-0 2019 Association of CYP2D6*10 (c. 100 C>T) genotype with Z-END Concentration in Patients with Breast Cancer Receiving Tamoxifen Therapy in Indonesian Population. Tamoxifen 116-125 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 15-21 30843495-1 2019 BACKGROUND: Tamoxifen (TAM) is a frequently used hormonal prodrug for patients with breast cancer that needs to be activated by cytochrome P450 2D6 (CYP2D6) into Zusammen-endoxifen (Z-END). Tamoxifen 12-21 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 128-147 30843495-1 2019 BACKGROUND: Tamoxifen (TAM) is a frequently used hormonal prodrug for patients with breast cancer that needs to be activated by cytochrome P450 2D6 (CYP2D6) into Zusammen-endoxifen (Z-END). Tamoxifen 12-21 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 149-155 30843495-1 2019 BACKGROUND: Tamoxifen (TAM) is a frequently used hormonal prodrug for patients with breast cancer that needs to be activated by cytochrome P450 2D6 (CYP2D6) into Zusammen-endoxifen (Z-END). Tamoxifen 23-26 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 128-147 30843495-1 2019 BACKGROUND: Tamoxifen (TAM) is a frequently used hormonal prodrug for patients with breast cancer that needs to be activated by cytochrome P450 2D6 (CYP2D6) into Zusammen-endoxifen (Z-END). Tamoxifen 23-26 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 149-155 30843495-10 2019 CONCLUSION: There was a significant association between CYP2D6*10 (c.100C>T) and attainment of plasma steady-state Z-END MTC in Indonesian breast cancer patients receiving TAM at a dose of 20 mg/day. Tamoxifen 175-178 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 56-62 29980881-2 2018 Tamoxifen is a prodrug and requires bioactivation by CYP2D6. Tamoxifen 0-9 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 53-59 30526633-3 2018 CYP2D6 is a key enzyme in the metabolism of tamoxifen to its active metabolites, and variants in this gene have been associated with reduced tamoxifen metabolism. Tamoxifen 44-53 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 30526633-3 2018 CYP2D6 is a key enzyme in the metabolism of tamoxifen to its active metabolites, and variants in this gene have been associated with reduced tamoxifen metabolism. Tamoxifen 141-150 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 30526633-12 2018 CONCLUSION: This study suggests that the CYP2D6 phenotype may contribute to some of the observed variability in the impact of tamoxifen treatment for a first breast cancer on risk of developing CBC. Tamoxifen 126-135 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 41-47 30536272-0 2018 Impacts of Cytochrome P450 2D6 (CYP2D6) Genetic Polymorphism in Tamoxifen Therapy for Breast Cancer. Tamoxifen 64-73 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 11-30 30536272-0 2018 Impacts of Cytochrome P450 2D6 (CYP2D6) Genetic Polymorphism in Tamoxifen Therapy for Breast Cancer. Tamoxifen 64-73 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 32-38 30536272-2 2018 An important barrier to the use of TMX is the development of drug resistance caused by molecular processes related to genetic and epigenetic mechanisms, such as the actions of cytochrome P450 2D6 (CYP2D6) polymorphisms and of its metabolites. Tamoxifen 35-38 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 176-195 30536272-7 2018 The CYP2D6 gene seems to contribute to decreasing the efficacy of TMX, while the main mechanism responsible for therapy failure, morbidity, and mortality is the progression of the disease. Tamoxifen 66-69 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 4-10 30352838-5 2018 CYP2D6 was genotyped in subjects taking tamoxifen to study the association with menopausal symptoms. Tamoxifen 40-49 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 30352838-8 2018 Compared with the slow metabolizers, a higher percentage of subjects with CYP2D6 extensive metabolizer genotype complained of a >=3 score in the vasomotor, psychosocial, and sexual domain in the tamoxifen arms (P value = 0.01, 0.007, and 0.007, respectively). Tamoxifen 198-207 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 74-80 29978573-2 2018 TOR might have a therapeutic advantage in certain subgroups of patients, such as Chinese women with the CYP2D6 *10 (c.100C > T) T/T genotype, who would get less benefit when receiving adjuvant TAM treatment. Tamoxifen 196-199 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 104-110 29978573-9 2018 The advantage of adjuvant TOR over TAM in Chinese breast cancer patients might be caused by the significant benefit obtained by the CYP2D6 *10 T/T patients, who accounted for one-fifth of the overall population. Tamoxifen 35-38 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 132-138 30345040-0 2018 CYP2D6*3 (A2549del), *4 (G1846A), *10 (C100T) and *17 (C1023T) genetic polymorphisms in Iranian breast cancer patients treated with adjuvant tamoxifen. Tamoxifen 141-150 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 30345040-1 2018 There is controversy regarding the efficacy of tamoxifen in breast cancer patients who are carriers of cytochrome P450 2D6 (CYP2D6) gene polymorphisms. Tamoxifen 47-56 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 103-122 30345040-1 2018 There is controversy regarding the efficacy of tamoxifen in breast cancer patients who are carriers of cytochrome P450 2D6 (CYP2D6) gene polymorphisms. Tamoxifen 47-56 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 124-130 30345040-11 2018 This finding may affect the selection of an optimal hormone therapy, as patients with low CYP2D6 pathway activity may not sufficiently convert tamoxifen to its active metabolite endoxifen. Tamoxifen 143-152 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 90-96 29396856-0 2018 The relationship between the CYP2D6 polymorphisms and tamoxifen efficacy in adjuvant endocrine therapy of breast cancer patients in Chinese Han population. Tamoxifen 54-63 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 29-35 29920987-0 2018 Application of PBPK Modeling and Virtual Clinical Study Approaches to Predict the Outcomes of CYP2D6 Genotype-Guided Dosing of Tamoxifen. Tamoxifen 127-136 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 94-100 29920987-1 2018 The Tamoxifen Response by CYP2D6 Genotype-based Treatment-1 (TARGET-1) study (n = 180) was conducted from 2012-2017 in Japan to determine the efficacy of tamoxifen dosing guided by cytochrome P450 2D6 (CYP2D6) genotypes. Tamoxifen 4-13 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 26-32 29920987-3 2018 Our analyses indicated that the expected probability to achieve the end point (demonstrating the superior efficacy of the escalated tamoxifen dose over the standard dose in patients carrying CYP2D6 variants) was 0.469 on average. Tamoxifen 132-141 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 191-197 29637493-2 2018 Since cytochrome P450 (CYP) 2D6 is the most important enzyme in the production of endoxifen, drugs that inhibit CYP2D6 would be expected to reduce tamoxifen efficacy. Tamoxifen 147-156 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 6-31 29637493-2 2018 Since cytochrome P450 (CYP) 2D6 is the most important enzyme in the production of endoxifen, drugs that inhibit CYP2D6 would be expected to reduce tamoxifen efficacy. Tamoxifen 147-156 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 112-118 29637493-4 2018 Although the clinical evidence on the impact of CYP2D6 inhibitors on tamoxifen efficacy is mixed, there were serious flaws in many of the studies. Tamoxifen 69-78 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 48-54 29637493-5 2018 Thus, there is a reasonable chance that CYP2D6 inhibitors do in fact inhibit tamoxifen efficacy. Tamoxifen 77-86 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 40-46 29637493-8 2018 Based on current clinical evidence, one could argue that enzyme inducers are potentially more dangerous than CYP2D6 inhibitors in patients taking tamoxifen. Tamoxifen 146-155 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 109-115 29637493-9 2018 Moreover, early evidence suggests that the combination of CYP2D6 inhibitors plus enzyme inducers may produce catastrophic inhibition of tamoxifen efficacy. Tamoxifen 136-145 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 58-64 30022682-0 2018 Effect of CYP2C19 and CYP2D6 genotype on tamoxifen treatment outcome indicates endogenous and exogenous interplay. Tamoxifen 41-50 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 22-28 30022682-5 2018 We hypothesize that poor bioactivation of tamoxifen in patients with low CYP2D6 activity and high CYP2C19 metabolism represents a tamoxifen-treated patient group that has the worst clinical outcome. Tamoxifen 42-51 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 73-79 30022682-5 2018 We hypothesize that poor bioactivation of tamoxifen in patients with low CYP2D6 activity and high CYP2C19 metabolism represents a tamoxifen-treated patient group that has the worst clinical outcome. Tamoxifen 130-139 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 73-79 29396856-1 2018 Variants of the CYP2D6 gene may lead to a poor prognosis of tamoxifen (TAM)-treated patients. Tamoxifen 60-69 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 16-22 29396856-1 2018 Variants of the CYP2D6 gene may lead to a poor prognosis of tamoxifen (TAM)-treated patients. Tamoxifen 71-74 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 16-22 29396856-2 2018 Our study validated the association between the CYP2D6 genotype and outcomes of patients receiving TAM in adjuvant endocrine therapy. Tamoxifen 99-102 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 48-54 29396856-7 2018 Among the 325 patients who received TAM, the 5-year DFS rate was considerably lower in CYP2D6*10 T/T genotype patients than C/C or C/T patients (54.9% vs. 70.9%, p = 0.007). Tamoxifen 36-39 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 87-93 29801584-3 2018 Genetic polymorphisms that confer reduced CYP2D6 activity or concurrent use of CYP2D6-inhibiting drugs may reduce the clinical efficacy of tamoxifen. Tamoxifen 139-148 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 42-48 29436156-4 2018 Only the CYP2D6 variation was significantly associated with concentrations of endoxifen (P = 0.0008) and 4-hydroxytamoxifen (P = 0.0074), tamoxifen"s principal active metabolites, as well as key metabolic ratios. Tamoxifen 114-123 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 9-15 29436156-6 2018 In AIAN populations, CYP2D6 is the largest contributor to tamoxifen bioactivation, illustrating the importance of validating pharmacogenetic testing for therapy optimization in an understudied population. Tamoxifen 58-67 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 21-27 29320849-5 2018 Finally, as an illustrative example, the relative contribution of the three primary oxidation routes of tamoxifen was rationalized through energetic barriers obtained from density functional calculations and docking experiments involving CYP3A4 and CYP2D6 isoforms. Tamoxifen 104-113 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 249-255 28540639-2 2018 This study used a modelling and simulation approach to quantitatively assess the influence of cytochrome P450 (CYP) 2D6 activity and other relevant factors on tamoxifen and endoxifen PK to identify subgroups at risk for subtherapeutic endoxifen concentrations. Tamoxifen 159-168 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 94-119 29385237-1 2018 Tamoxifen is biotransformed by CYP2D6 to 4-hydroxytamoxifen and 4-hydroxy N-desmethyl tamoxifen (endoxifen), both with greater antiestrogenic potency than the parent drug. Tamoxifen 0-9 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 31-37 29385237-2 2018 Patients with certain CYP2D6 genetic polymorphisms and patients who receive strong CYP2D6 inhibitors exhibit lower endoxifen concentrations and a higher risk of disease recurrence in some studies of tamoxifen adjuvant therapy of early breast cancer. Tamoxifen 199-208 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 22-28 29385237-2 2018 Patients with certain CYP2D6 genetic polymorphisms and patients who receive strong CYP2D6 inhibitors exhibit lower endoxifen concentrations and a higher risk of disease recurrence in some studies of tamoxifen adjuvant therapy of early breast cancer. Tamoxifen 199-208 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 83-89 29385237-3 2018 We summarize evidence from the literature and provide therapeutic recommendations for tamoxifen based on CYP2D6 genotype. Tamoxifen 86-95 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 105-111 28762370-10 2018 Furthermore, additional clinical research is warranted to determine whether patients with CYP2D6 PM phenotypes or low endoxifen levels will have better clinical outcomes with increased tamoxifen dosing compared to standard dosing. Tamoxifen 185-194 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 90-96 29479969-2 2018 TAM is metabolized by cytochrome P450 (CYP450) enzymes,including CYP2D6, CYP3A5 and CYP2C19, whose genetic variations may have clinicopathological importance.However, reports on the association of various P450 polymorphisms with certain cancers are contradictory. Tamoxifen 0-3 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 65-71 29801584-3 2018 Genetic polymorphisms that confer reduced CYP2D6 activity or concurrent use of CYP2D6-inhibiting drugs may reduce the clinical efficacy of tamoxifen. Tamoxifen 139-148 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 79-85 29801584-5 2018 In this chapter, we outline tamoxifen"s clinical pharmacology and give an overview of the research to date on the association between CYP2D6 inhibition and tamoxifen effectiveness. Tamoxifen 156-165 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 134-140 28877533-1 2017 OBJECTIVES: Tamoxifen bioactivation to endoxifen is mediated primarily by CYP2D6; however, considerable variability remains unexplained. Tamoxifen 12-21 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 74-80 29245979-8 2017 CYP2D6 AS was the only variable that showed associations with both metabolite concentration and ratio: endoxifen (P < 0.001), NDM (P < 0.001), endoxifen/NDM (P < 0.001), NDM/tamoxifen (P < 0.001), and 4-OH tamoxifen/tamoxifen (P = 0.005). Tamoxifen 183-192 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 29245979-8 2017 CYP2D6 AS was the only variable that showed associations with both metabolite concentration and ratio: endoxifen (P < 0.001), NDM (P < 0.001), endoxifen/NDM (P < 0.001), NDM/tamoxifen (P < 0.001), and 4-OH tamoxifen/tamoxifen (P = 0.005). Tamoxifen 218-227 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 29180876-0 2017 The effect of CYP2D6 *10 polymorphism on adjuvant tamoxifen in Asian breast cancer patients: a meta-analysis. Tamoxifen 50-59 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 14-20 29180876-1 2017 Objective: To evaluate the effect of CYP2D6 *10 polymorphism (C 100C>T, rs1065852) on clinical outcomes of female Asian breast cancer patients with tamoxifen adjuvant treatment. Tamoxifen 151-160 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 37-43 28730340-1 2017 PURPOSE: A number of studies have tested the hypothesis that breast cancer patients with low-activity CYP2D6 genotypes achieve inferior benefit from tamoxifen treatment, putatively due to lack of metabolic activation to endoxifen. Tamoxifen 149-158 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 102-108 28730340-11 2017 These contradictory findings suggest that the association between CYP2D6 genotype and tamoxifen treatment efficacy is null or near null, and unlikely to be useful in clinical practice. Tamoxifen 86-95 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 66-72 28592184-1 2017 Letter in resonse to: Del Re M, Rofi E, Citi V, Fidilio L, Danesi R. Should CYP2D6 be genotyped when treating with tamoxifen? Tamoxifen 115-124 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 76-82 29135105-1 2017 PURPOSE: This study was designed to evaluate the effect of CYP2D6 and ABCB1 polymorphisms and co-medication on the outcomes and adverse events (AEs) of tamoxifen therapy. Tamoxifen 152-161 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 59-65 28369967-0 2017 A Simulation Study to Compare the Treatment Effect of Tamoxifen by CYP2D6 Genotypes and Third-Generation Aromatase Inhibitors. Tamoxifen 54-63 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 67-73 28369967-7 2017 Subsequently, DFS HRs of AIs versus tamoxifen by CYP2D6 genotypes (HRAI/TAM,W for EMs, HRAI/TAM,V for IMs/PMs) were estimated via regression analyses using NONMEM, based on the simulated genotype distributions, HRV/W,TAM , and HRs, of AIs versus tamoxifen (HRAI/TAM ) reported in the ATAC and BIG 1-98 trials. Tamoxifen 36-45 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 49-55 28369967-10 2017 These results suggest that in patients with the CYP2D6 genotype representing EMs, the treatment effect of tamoxifen is comparable to that of AIs. Tamoxifen 106-115 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 48-54 28955222-0 2017 Improved Prediction of Endoxifen Metabolism by CYP2D6 Genotype in Breast Cancer Patients Treated with Tamoxifen. Tamoxifen 102-111 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 47-53 28955222-13 2017 Conclusion: The CYP2D6 explanatory power for active drug level assessment is maximized by TAM-specific phenotype assignments while a genotype cutoff that separates PM/PM and PM/IM from the remaining patients may improve clinical benefit via increased endoxifen concentrations. Tamoxifen 90-93 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 16-22 29135105-0 2017 Impact of ABCB1 and CYP2D6 polymorphisms on tamoxifen treatment outcomes and adverse events in breast cancer patients. Tamoxifen 44-53 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 20-26 28593824-0 2017 Should CYP2D6 be genotyped when treating with tamoxifen? Tamoxifen 46-55 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 7-13 28593824-1 2017 Letter in regards to: Del Re M, Rofi E, Citi V, Fidilio L, Danesi R. Should CYP2D6 be genotyped when treating with tamoxifen? Tamoxifen 115-124 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 76-82 28382001-3 2017 PBPK modeling was applied to demonstrate the impact of drug holidays on plasma levels of tamoxifen and its active metabolite endoxifen for different CYP2D6 genotypes. Tamoxifen 89-98 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 149-155 28450788-0 2017 Effects of CYP2D6 and CYP3A5 polymorphisms on tamoxifen and its metabolites in Thai breast cancer patients. Tamoxifen 46-55 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 11-17 28450788-1 2017 PURPOSE: This study aimed to determine the effects of CYP2D6 and CYP3A5 polymorphisms on the levels of tamoxifen (TAM) and its metabolites in the plasma of breast cancer patients. Tamoxifen 103-112 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 54-60 28450788-1 2017 PURPOSE: This study aimed to determine the effects of CYP2D6 and CYP3A5 polymorphisms on the levels of tamoxifen (TAM) and its metabolites in the plasma of breast cancer patients. Tamoxifen 114-117 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 54-60 28450788-2 2017 The protocol was designed to test the associations between CYP2D6, CYP3A5 genotypes and phenotypes (extensive metabolizer [EM], intermediate metabolizer [IM] and poor metabolizer [PM]) and TAM, N-desmethyl tamoxifen (NDMT), endoxifen (END) and 4-hydroxytamoxifen (4OHT) concentrations. Tamoxifen 189-192 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 59-65 28671087-0 2017 The effect analysis of CYP2D6 gene polymorphism in the toremifene and tamoxifen treatment in patient with breast cancer. Tamoxifen 70-79 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 23-29 28671087-1 2017 The purpose of the present research work was to study the CYP2D6 gene polymorphism survival outcome after breast cancer patient received the toremifene and tamoxifen treatment. Tamoxifen 156-165 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 58-64 28671087-11 2017 In summary, CYP2D6 gene polymorphism relates with the effect of toremifene and tamoxifen treatment in patient with ER positive breast cancer and null allele homozygote CYP2D6*10/*10 can lead to a poor prognosis. Tamoxifen 79-88 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 12-18 28671087-11 2017 In summary, CYP2D6 gene polymorphism relates with the effect of toremifene and tamoxifen treatment in patient with ER positive breast cancer and null allele homozygote CYP2D6*10/*10 can lead to a poor prognosis. Tamoxifen 79-88 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 168-174 27797974-0 2017 Significant Effect of Polymorphisms in CYP2D6 on Response to Tamoxifen Therapy for Breast Cancer: A Prospective Multicenter Study. Tamoxifen 61-70 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 39-45 27797974-1 2017 Purpose: CYP2D6 is the key enzyme responsible for the generation of the potent active metabolite of tamoxifen, "endoxifen." Tamoxifen 100-109 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 9-15 27797974-2 2017 There are still controversial reports questioning the association between CYP2D6 genotype and tamoxifen efficacy. Tamoxifen 94-103 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 74-80 27797974-7 2017 Although CYP2D6 variants were not associated with pathologic response nor hot flushes, they showed significant association with Ki-67 response after preoperative tamoxifen therapy (P = 0.018; between two groups, one with at least one wild-type allele and the other without a wild-type allele).Conclusions: This is the first prospective study evaluating the relationship between CYP2D6 variants and Ki-67 response after tamoxifen therapy. Tamoxifen 162-171 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 9-15 27797974-7 2017 Although CYP2D6 variants were not associated with pathologic response nor hot flushes, they showed significant association with Ki-67 response after preoperative tamoxifen therapy (P = 0.018; between two groups, one with at least one wild-type allele and the other without a wild-type allele).Conclusions: This is the first prospective study evaluating the relationship between CYP2D6 variants and Ki-67 response after tamoxifen therapy. Tamoxifen 419-428 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 9-15 27797974-8 2017 Our results suggest that genetic variation in CYP2D6 is a key predictor for the response to tamoxifen in patients with breast cancer. Tamoxifen 92-101 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 46-52 28382001-4 2017 Materials and Methods: A virtual study with 24,000 patients was conducted in order to investigate the development of tamoxifen steady-state kinetics in patient groups of different CYP2D6 genotypes. Tamoxifen 117-126 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 180-186 28403774-5 2017 METHODS: Lessons learnt from the association between tamoxifen and CYP2D6 genotyping were applied to identify polymorphisms with the potential to change clinical decision-making in patients on aromatase inhibitors. Tamoxifen 53-62 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 67-73 27698402-0 2017 Tamoxifen metabolism in breast cancer treatment: Taking the focus off the CYP2D6 gene. Tamoxifen 0-9 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 74-80 27988492-2 2017 Cytochrome P-450 2D6, encoded by the polymorphic cytochrome P-450 2D6 gene (CYP2D6), oxidizes tamoxifen to its most active metabolites. Tamoxifen 94-103 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 76-82 28293118-0 2017 CYP2D6 polymorphisms may predict occurrence of adverse effects to tamoxifen: a preliminary retrospective study. Tamoxifen 66-75 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 28293118-3 2017 Allelic variations altering the activity of cytochrome P450-2D6 enzyme affect response to tamoxifen by modulating metabolism of tamoxifen into its pharmacologically active metabolite endoxifen. Tamoxifen 90-99 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 44-63 28293118-3 2017 Allelic variations altering the activity of cytochrome P450-2D6 enzyme affect response to tamoxifen by modulating metabolism of tamoxifen into its pharmacologically active metabolite endoxifen. Tamoxifen 128-137 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 44-63 28293118-4 2017 Although association between CYP2D6 polymorphisms and recurrence of breast cancer in patients on tamoxifen had been reported, little evidence exists on association between these polymorphisms and adverse effects to tamoxifen. Tamoxifen 97-106 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 29-35 28293118-5 2017 This study explored the association between CYP2D6 polymorphisms and tamoxifen effects, hitherto not studied in Sri Lanka. Tamoxifen 69-78 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 44-50 28293118-13 2017 CONCLUSIONS: CYP2D6 SNP combination 2988G>A, -1584C and 2850C>T, strongly suggestive of *41 reduced functional allele, is likely to be useful in predicting occurrence of adverse effect fatty liver in breast cancer patients on tamoxifen, thereby alternative treatment can be considered and lifestyle modifications implemented. Tamoxifen 232-241 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 13-19 27988492-0 2017 Cytochrome P-450 2D6 (CYP2D6) Genotype and Breast Cancer Recurrence in Tamoxifen-Treated Patients: Evaluating the Importance of Loss of Heterozygosity. Tamoxifen 71-80 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-20 27988492-0 2017 Cytochrome P-450 2D6 (CYP2D6) Genotype and Breast Cancer Recurrence in Tamoxifen-Treated Patients: Evaluating the Importance of Loss of Heterozygosity. Tamoxifen 71-80 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 22-28 27988492-2 2017 Cytochrome P-450 2D6, encoded by the polymorphic cytochrome P-450 2D6 gene (CYP2D6), oxidizes tamoxifen to its most active metabolites. Tamoxifen 94-103 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-20 27988492-2 2017 Cytochrome P-450 2D6, encoded by the polymorphic cytochrome P-450 2D6 gene (CYP2D6), oxidizes tamoxifen to its most active metabolites. Tamoxifen 94-103 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 49-69 28403774-7 2017 RESULTS: Methodological flaws in major randomised controlled trials and continued referral to incorrect results in expert consensus statements are important factors delaying the implementation of CYP2D6 pharmacogenetics in tamoxifen treatment. Tamoxifen 223-232 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 196-202 28403774-9 2017 CONCLUSION: The clinical utility of CYP2D6 genotyping is well-established in patients at increased risk of tamoxifen resistance due to cumulative risk. Tamoxifen 107-116 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 36-42 27198207-4 2016 We compared the concentrations of tamoxifen and metabolites in 116 breast cancer patients with predicted phenotypes for CYP2D6, CYP3A4, CYP3A5, CYP2C9, CYP2C19, and ABCB1 genotypes. Tamoxifen 34-43 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 120-126 27632988-7 2017 CONCLUSION: CYP2D6 binding subsite A was found to be relatively selective for small molecular weight with higher polarity compared with subsite B which tends to favor larger molecular weight and relatively hydrophobic molecules such as tamoxifen and imipramine. Tamoxifen 236-245 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 12-18 27756789-0 2017 Application of Mice Humanized for CYP2D6 to the Study of Tamoxifen Metabolism and Drug-Drug Interaction with Antidepressants. Tamoxifen 57-66 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 34-40 27756789-3 2017 Antidepressants (ADs), which are often coprescribed to patients receiving tamoxifen, are also metabolized by CYP2D6 and evidence suggests that a drug-drug interaction between these agents adversely affects the outcome of tamoxifen therapy by inhibiting endoxifen formation. Tamoxifen 221-230 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 109-115 27198207-5 2016 A significant correlation between CYP2D6 phenotypes and tamoxifen metabolites was seen, strongest for endoxifen (P < .0001). Tamoxifen 56-65 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 34-40 27882219-0 2016 CYP2D6 gene polymorphisms in Brazilian patients with breast cancer treated with adjuvant tamoxifen and its association with disease recurrence. Tamoxifen 89-98 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 27907164-0 2016 Correction: National Prociency Testing Result of CYP2D6*10 Genotyping for Adjuvant Tamoxifen Therapy in China. Tamoxifen 83-92 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 49-55 27924964-0 2016 Frequency of CYP2D6*10 genotypes in Pakistani breast cancer patients taking adjuvant tamoxifen. Tamoxifen 85-94 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 13-19 27883289-0 2016 Should CYP2D6 be genotyped when treating with tamoxifen? Tamoxifen 46-55 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 7-13 27882219-1 2016 At present, there is controversy regarding the efficacy of tamoxifen in breast cancer patients who are carriers of cytochrome P450 2D6 (CYP2D6) gene polymorphisms, in terms of recurrence and overall survival. Tamoxifen 59-68 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 115-134 27882219-1 2016 At present, there is controversy regarding the efficacy of tamoxifen in breast cancer patients who are carriers of cytochrome P450 2D6 (CYP2D6) gene polymorphisms, in terms of recurrence and overall survival. Tamoxifen 59-68 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 136-142 27882219-8 2016 The present study concluded that the CYP2D6 gene polymorphism in women with hormone-sensitive breast cancer treated with tamoxifen was not associated with disease recurrence. Tamoxifen 121-130 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 37-43 27694571-1 2016 OBJECTIVE: To compare differences in mortality between women concomitantly treated with tamoxifen and selective serotonin reuptake inhibitors (SSRIs) that are potent inhibitors of the cytochrome-P450 2D6 enzyme (CYP2D6) versus tamoxifen and other SSRIs. Tamoxifen 89-98 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 185-204 27538915-0 2016 Rifampin-Mediated Induction of Tamoxifen Metabolism in a Humanized PXR-CAR-CYP3A4/3A7-CYP2D6 Mouse Model. Tamoxifen 31-40 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 86-92 27538915-3 2016 In humans, tamoxifen is metabolized primarily by CYP3A4 and CYP2D6, and multiple-day treatment with rifampin decreased tamoxifen exposure by 6.2-fold. Tamoxifen 11-20 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 60-66 28074989-2 2016 Endoxifen is a Tmf metabolite generated by cytochrome P450 2D6 (CYP2D6). Tamoxifen 15-18 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 43-62 28074989-2 2016 Endoxifen is a Tmf metabolite generated by cytochrome P450 2D6 (CYP2D6). Tamoxifen 15-18 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 64-70 28074989-8 2016 Tricyclic AD, paroxetine and fluoxetine should be avoided in patients receiving Tmf, because they are strong inhibitors of CYP2D6. Tamoxifen 80-83 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 123-129 27694571-1 2016 OBJECTIVE: To compare differences in mortality between women concomitantly treated with tamoxifen and selective serotonin reuptake inhibitors (SSRIs) that are potent inhibitors of the cytochrome-P450 2D6 enzyme (CYP2D6) versus tamoxifen and other SSRIs. Tamoxifen 89-98 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 213-219 27603206-0 2016 National Prociency Testing Result of CYP2D6*10 Genotyping for Adjuvant Tamoxifen Therapy in China. Tamoxifen 71-80 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 37-43 27603206-2 2016 Cytochrome P450 2D6 (CYP2D6) plays a key role in the process of metabolizing tamoxifen to its active moiety, endoxifen. Tamoxifen 77-86 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-19 27603206-2 2016 Cytochrome P450 2D6 (CYP2D6) plays a key role in the process of metabolizing tamoxifen to its active moiety, endoxifen. Tamoxifen 77-86 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 21-27 27603206-3 2016 Patients with variants of the CYP2D6 gene may not receive the full benefit of tamoxifen treatment. Tamoxifen 78-87 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 30-36 27603206-4 2016 The CYP2D6*10 variant (the most common variant in Asians) was analyzed to optimize the prescription of tamoxifen in China. Tamoxifen 103-112 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 4-10 27540311-0 2016 Prevalence of CYP2D6*2, CYP2D6*4, CYP2D6*10, and CYP3A5*3 in Thai breast cancer patients undergoing tamoxifen treatment. Tamoxifen 100-109 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 14-20 27474731-8 2016 The administration of potent CYP2D6 inhibitors leads to a diminished efficacy of tamoxifen because one of its most important active metabolites-endoxifen-is not sufficiently available. Tamoxifen 81-90 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 29-35 27648149-0 2016 Association of CYP2D6*10 (c.100C>T) polymorphisms with clinical outcome of breast cancer after tamoxifen adjuvant endocrine therapy in Chinese population. Tamoxifen 98-107 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 15-21 29924509-5 2016 Genetic polymorphisms of CYP2D6 and CYP3A4 will influence the plasma concentrations of active TAM metabolites and clinical outcomes for breast cancer patients treated with TAM. Tamoxifen 94-97 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 25-31 29924509-5 2016 Genetic polymorphisms of CYP2D6 and CYP3A4 will influence the plasma concentrations of active TAM metabolites and clinical outcomes for breast cancer patients treated with TAM. Tamoxifen 172-175 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 25-31 27540311-3 2016 This study aimed to explore the prevalence of the incomplete functional alleles and genotypes of the CYP2D6 and CYP3A5 genes in Thai breast cancer patients undergoing TAM treatment. Tamoxifen 167-170 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 101-107 27484880-0 2016 A pooled analysis of CYP2D6 genotype in breast cancer prevention trials of low-dose tamoxifen. Tamoxifen 84-93 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 21-27 27484880-1 2016 Decreased CYP2D6 activity is associated with lower levels of active tamoxifen metabolites. Tamoxifen 68-77 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 10-16 27484880-9 2016 CYP2D6 genotype may have an impact on tamoxifen efficacy at low doses. Tamoxifen 38-47 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 27226358-12 2016 IMPLICATIONS FOR PRACTICE: This secondary analysis of a prospective CYP2D6 genotype-guided tamoxifen dose escalation study confirms that escalation to 40 mg/day in patients with low-activity CYP2D6 phenotypes (poor or intermediate metabolizers) increases endoxifen concentrations without any obvious increases in treatment-related toxicity. Tamoxifen 91-100 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 68-74 27249031-0 2016 One step at a time: CYP2D6 guided tamoxifen treatment awaits convincing evidence of clinical validity. Tamoxifen 34-43 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 20-26 27226358-0 2016 Tamoxifen Dose Escalation in Patients With Diminished CYP2D6 Activity Normalizes Endoxifen Concentrations Without Increasing Toxicity. Tamoxifen 0-9 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 54-60 27226358-1 2016 BACKGROUND: Polymorphic CYP2D6 is primarily responsible for metabolic activation of tamoxifen to endoxifen. Tamoxifen 84-93 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 24-30 27226358-2 2016 We previously reported that by increasing the daily tamoxifen dose to 40 mg/day in CYP2D6 intermediate metabolizer (IM), but not poor metabolizer (PM), patients achieve endoxifen concentrations similar to those of extensive metabolizer patients on 20 mg/day. Tamoxifen 52-61 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 83-89 27109434-0 2016 Functional characterization of 22 novel CYP2D6 variants for the metabolism of Tamoxifen. Tamoxifen 78-87 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 40-46 27109434-1 2016 OBJECTIVES: This study aimed to assess the catalytic characteristics of 24 CYP2D6 allelic isoforms found in Chinese Han population on the metabolism of tamoxifen in vitro. Tamoxifen 152-161 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 75-81 27109434-2 2016 METHODS: Recombinant CYP2D6 microsomes of distinguished genotypes were used to characterize the corresponding enzyme activity towards tamoxifen. Tamoxifen 134-143 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 21-27 27109434-5 2016 CONCLUSION: The comprehensive assessment of CYP2D6 variants provides significant insights into allele-specific activity towards tamoxifen in vitro, suggesting that most of the carriers of these alleles might be paid more attention when using CYP2D6-mediated drugs clinically. Tamoxifen 128-137 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 44-50 27109434-5 2016 CONCLUSION: The comprehensive assessment of CYP2D6 variants provides significant insights into allele-specific activity towards tamoxifen in vitro, suggesting that most of the carriers of these alleles might be paid more attention when using CYP2D6-mediated drugs clinically. Tamoxifen 128-137 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 242-248 27169677-1 2016 BACKGROUND: Tamoxifen, a common anti-estrogen breast cancer medication, is a prodrug that undergoes bioactivation via cytochrome P450 enzymes, CYP2D6 and to a lesser degree, CYP3A4 to form the active metabolite endoxifen. Tamoxifen 12-21 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 143-149 26446141-1 2016 BACKGROUND AND OBJECTIVE: The anti-oestrogen tamoxifen requires metabolic activation to endoxifen by cytochrome P450 (CYP) enzymes, predominantly CYP2D6. Tamoxifen 45-54 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 146-152 26896706-0 2016 Design and synthesis of novel tamoxifen analogues that avoid CYP2D6 metabolism. Tamoxifen 30-39 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 61-67 26896706-2 2016 TAM is metabolized to the more active 4-hydroxytamoxifen (4-OH-TAM) and endoxifen by cytochrome P450 (CYP) mainly CYP2D6 and CYP3A4 enzymes. Tamoxifen 0-3 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 114-120 26896706-3 2016 Due to the genetic polymorphisms in CYP2D6 genes, high variation in the clinical outcomes of TAM treatment is observed among women of different populations. Tamoxifen 93-96 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 36-42 27060675-2 2016 In favour of preemptive evaluation of phenotypic profile of patients is the strong pharmacologic rationale, being that the formation of endoxifen, the major and clinically most important metabolite of tamoxifen, is largely dependent on the activity of CYP2D6. Tamoxifen 201-210 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 252-258 27060675-5 2016 Despite this, the CYP2D6 genotyping test for tamoxifen is available in many laboratories and it may still be an appropriate test to use it in specific cases. Tamoxifen 45-54 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 18-24 27043475-0 2016 Evaluating the impact of missenses mutations in CYP2D6*7 and CYP2D6*14A: does it compromise tamoxifen metabolism? Tamoxifen 92-101 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 48-54 27043475-0 2016 Evaluating the impact of missenses mutations in CYP2D6*7 and CYP2D6*14A: does it compromise tamoxifen metabolism? Tamoxifen 92-101 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 61-67 26814364-1 2016 Tamoxifen, a hormonal therapy drug against estrogen receptor-positive breast cancer, can be metabolized by cytochrome P450 enzymes such as CYP3A4 and CYP3A5, and converted to N-desmethyltamoxifen, which is subsequently, metabolized by CYP2D6 and inverted to form 4-hydroxy-N-desmethyltamoxifen (endoxifen). Tamoxifen 0-9 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 235-241 26446141-2 2016 Potent CYP2D6-inhibiting antidepressants can seriously disrupt tamoxifen metabolism, probably influencing the efficacy of tamoxifen. Tamoxifen 63-72 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 7-13 26446141-2 2016 Potent CYP2D6-inhibiting antidepressants can seriously disrupt tamoxifen metabolism, probably influencing the efficacy of tamoxifen. Tamoxifen 122-131 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 7-13 26446141-4 2016 We investigated the effects of switching potent CYP2D6-inhibiting antidepressants to weak CYP2D6-inhibiting antidepressants on the plasma pharmacokinetics of tamoxifen. Tamoxifen 158-167 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 90-96 26510986-1 2016 The cytochrome P450, family 2, subfamily D, polypeptide 6 (CYP2D6) is an enzyme that is predominantly involved in the metabolism of tamoxifen. Tamoxifen 132-141 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 4-57 26987536-6 2016 Within each subsection a specific pharmacogenetic association is described in detail; CYP2D6-tamoxifen, BRCA-PARP inhibitors, and FCGRA-trastuzumab, respectively, followed by a general discussion of other less well-established examples or areas for further research. Tamoxifen 93-102 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 86-92 26510986-1 2016 The cytochrome P450, family 2, subfamily D, polypeptide 6 (CYP2D6) is an enzyme that is predominantly involved in the metabolism of tamoxifen. Tamoxifen 132-141 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 59-65 26510986-2 2016 Genetic polymorphisms of the CYP2D6 gene may contribute to inter-individual variability in tamoxifen metabolism, which leads to the differences in clinical response to tamoxifen among breast cancer patients. Tamoxifen 91-100 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 29-35 26510986-2 2016 Genetic polymorphisms of the CYP2D6 gene may contribute to inter-individual variability in tamoxifen metabolism, which leads to the differences in clinical response to tamoxifen among breast cancer patients. Tamoxifen 168-177 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 29-35 26510986-9 2016 In terms of CYP2D6 phenotype, 61.5% of Malaysian Malay breast cancer patients are predicted as extensive metabolizers in which they are most likely to respond well to tamoxifen therapy. Tamoxifen 167-176 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 12-18 25963137-2 2015 Previous studies, in women, tried to evaluate the impact of CYP2D6 polymorphisms in tamoxifen efficacy with conflicting results. Tamoxifen 84-93 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 60-66 29787014-0 2016 Polymorphism of the CYP2D6 gene in women with breast cancer treated with tamoxifen. Tamoxifen 73-82 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 20-26 29787014-1 2016 OBJECTIVE: To evaluate polymorphism frequency of the CYP2D6*4, *10, and * 17 alleles in women with breast cancer treated with tamoxifen. Tamoxifen 126-135 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 53-59 26898104-1 2016 BACKGROUND: Tamoxifen (TAM) is metabolized to the more active 4-hydroxytamoxifen by CYP2D6 enzyme. Tamoxifen 12-21 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 84-90 26898104-1 2016 BACKGROUND: Tamoxifen (TAM) is metabolized to the more active 4-hydroxytamoxifen by CYP2D6 enzyme. Tamoxifen 23-26 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 84-90 26898104-2 2016 Due to the genetic polymorphisms in CYP2D6, clinical outcomes of TAM treatment vary. Tamoxifen 65-68 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 36-42 26898104-7 2016 CONCLUSION: The novel analogs were more potent than TAM with higher selectivity toward ERalpha and with potential metabolic stability toward CYP2D6. Tamoxifen 52-55 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 141-147 25853922-0 2015 Influence of CYP2D6 and CYP3A4 Phenotypes, Drug Interactions, and Vitamin D Status on Tamoxifen Biotransformation. Tamoxifen 86-95 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 13-19 25853922-9 2015 Median plasma levels of TAM (161.50 ng mL) and HTF (1.32 ng mL) in CYP2D6 IM/CYP3A4 poor metabolizer patients were higher (P < 0.05) than those from CYP2D6 IM/CYP3A4 extensive metabolizer patients (122.07 ng mL and 0.61 ng mL, respectively). Tamoxifen 24-27 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 67-73 25853922-9 2015 Median plasma levels of TAM (161.50 ng mL) and HTF (1.32 ng mL) in CYP2D6 IM/CYP3A4 poor metabolizer patients were higher (P < 0.05) than those from CYP2D6 IM/CYP3A4 extensive metabolizer patients (122.07 ng mL and 0.61 ng mL, respectively). Tamoxifen 24-27 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 152-158 26369533-0 2015 CYP2D6 genotype- and endoxifen-guided tamoxifen dose escalation increases endoxifen serum concentrations without increasing side effects. Tamoxifen 38-47 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 26369533-1 2015 Breast cancer patients with absent or reduced CYP2D6 activity and consequently low endoxifen levels may benefit less from tamoxifen treatment. Tamoxifen 122-131 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 46-52 26369533-2 2015 CYP2D6 poor and intermediate metabolizers may need a personalized increased tamoxifen dose to achieve effective endoxifen serum concentrations, without increasing toxicity. Tamoxifen 76-85 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 26369533-3 2015 From a prospective study population of early breast cancer patients using tamoxifen (CYPTAM: NTR1509), 12 CYP2D6 poor and 12 intermediate metabolizers were selected and included in a one-step tamoxifen dose escalation study during 2 months. Tamoxifen 192-201 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 106-112 26369533-5 2015 Endoxifen levels and tamoxifen toxicity were determined at baseline and after 2 months, just before patients returned to the standard dose of 20 mg. Tamoxifen dose escalation in CYP2D6 poor and intermediate metabolizers significantly increased endoxifen concentrations (p < 0.001; p = 0.002, respectively) without increasing side effects. Tamoxifen 21-30 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 178-184 26369533-5 2015 Endoxifen levels and tamoxifen toxicity were determined at baseline and after 2 months, just before patients returned to the standard dose of 20 mg. Tamoxifen dose escalation in CYP2D6 poor and intermediate metabolizers significantly increased endoxifen concentrations (p < 0.001; p = 0.002, respectively) without increasing side effects. Tamoxifen 149-158 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 178-184 26369533-10 2015 CYP2D6 genotype- and endoxifen-guided tamoxifen dose escalation increased endoxifen concentrations without increasing short-term side effects. Tamoxifen 38-47 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 26423799-6 2015 Our results suggest that the potential contribution of CYP2D6 in the bioactivation pathway of TOR may be lower compared to TAM, and may have a different impact on clinical outcome than CYP2D6 polymorphisms. Tamoxifen 123-126 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 55-61 26232141-1 2015 BACKGROUND: Tamoxifen, the most frequently used drug for treating estrogen receptor-positive breast cancer, must be converted into active metabolites to exert its therapeutic efficacy, mainly through CYP2D6 enzymes. Tamoxifen 12-21 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 200-206 26232141-2 2015 The objective of this study was to investigate the impact of CYP2D6 polymorphisms on (Z)-endoxifen-directed tamoxifen metabolism and to assess the usefulness of CYP2D6 genotyping for identifying patients who are likely to have insufficient (Z)-endoxifen concentrations to benefit from standard therapy. Tamoxifen 108-117 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 61-67 26232141-10 2015 The CYP2D6 genotype accounted for plasma level variability of (Z)-endoxifen by 27 % (p < 10(-16)) and for the variability of metabolic ratio indicating (Z)-endoxifen-directed metabolism of tamoxifen by 51 % (p < 10(-43)). Tamoxifen 192-201 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 4-10 25940823-3 2015 Tamoxifen is bioactivated by cytochrome P450 (CYP) enzymes such as CYP2B6, CYP2C9, CYP2C19, CYP2D6 and CYP3A4/5, resulting in the formation of active metabolites, including 4-hydroxy-tamoxifen and endoxifen. Tamoxifen 0-9 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 92-98 26192892-0 2015 The Effect of Tamoxifen Dose Increment in Patients With Impaired CYP2D6 Activity. Tamoxifen 14-23 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 65-71 26192892-1 2015 BACKGROUND: The effect of tamoxifen dose elevation on endoxifen serum concentration was investigated in patients with reduced CYP2D6 activity resulting from genetic variation and/or CYP2D6 inhibitor use. Tamoxifen 26-35 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 126-132 26071758-1 2015 As a prodrug, tamoxifen is activated by the P450 enzyme CYP2D6 that is responsible for converting it to the active metabolites, 4-hydroxytamoxifen and endoxifen. Tamoxifen 14-23 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 56-62 26203310-8 2015 CYP2D6 allelic variants produce variable rates of tamoxifen metabolism and are associated with survival outcomes. Tamoxifen 50-59 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 25554091-7 2015 Variants in CYP2D6 are associated with altered metabolism tamoxifen; however, current data do not support widespread clinical testing. Tamoxifen 58-67 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 12-18 25943764-7 2015 These alterations in the metabolism profile resulted in significantly reduced drug-drug interactions between CTP-347 and two other CYP2D6-metabolized drugs: tamoxifen (in vitro) and dextromethorphan (in humans). Tamoxifen 157-166 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 131-137 25714002-0 2015 Evaluation of CYP2D6 enzyme activity using a 13C-dextromethorphan breath test in women receiving adjuvant tamoxifen. Tamoxifen 106-115 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 14-20 25714002-1 2015 BACKGROUND: In tamoxifen-treated patients, breast cancer recurrence differs according to CYP2D6 genotype and endoxifen steady-state concentrations (Endx Css). Tamoxifen 15-24 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 89-95 25891764-0 2015 Further characterization of a 13C-dextromethorphan breath test for CYP2D6 phenotyping in breast cancer patients on tamoxifen therapy. Tamoxifen 115-124 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 67-73 25891764-1 2015 In a previous study, we found that the CYP2D6 phenotype determined by (13)C-dextromethorphan breath test (DM-BT) might be used to predict tamoxifen treatment outcome in breast cancer patients in the adjuvant setting. Tamoxifen 138-147 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 39-45 25638249-0 2015 Loss of heterozygosity at the CYP2D6 locus in breast cancer: implications for tamoxifen pharmacogenetic studies. Tamoxifen 78-87 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 30-36 25618289-0 2015 Individualization of tamoxifen therapy: much more than just CYP2D6 genotyping. Tamoxifen 21-30 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 60-66 25618289-2 2015 The principal active metabolite - endoxifen - is generated through hepatic metabolism of tamoxifen, with key roles for cytochrome P450 (CYP) CYP2D6 and CYP3A. Tamoxifen 89-98 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 141-147 25618289-3 2015 By influencing endoxifen formation, genetic variants of CYP2D6 may affect response to tamoxifen. Tamoxifen 86-95 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 56-62 25618289-6 2015 Genetic variants of other CYP enzymes, including CYP3A4 and CYP2C9/19, as well as co-medication interfering with the metabolic activity of CYP2D6 and CYP3A4 have been shown to affect endoxifen concentrations and may also contribute to the variability in response to tamoxifen. Tamoxifen 266-275 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 139-145 25743120-0 2015 Genetic polymorphisms of CYP2D6*10 and the effectiveness of combined tamoxifen citrate and testosterone undecanoate treatment in infertile men with idiopathic oligozoospermia. Tamoxifen 69-86 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 25-31 25712191-2 2015 Because CYP2D6 is known to be an important enzyme responsible for the generation of the potent tamoxifen metabolite, "endoxifen", lots of studies reported that genetic variation which reduced its enzyme activity were associated with poor clinical outcome of breast cancer patients treated with tamoxifen. Tamoxifen 294-303 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 8-14 26434912-0 2015 CYP2D6 Genotype and Risk of Recurrence in Tamoxifen Treated Breast Cancer Patients. Tamoxifen 42-51 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 26434912-1 2015 BACKGROUND: Despite consistent pharmacogenetic effects of CYP2D6 on tamoxifen exposure, there is considerable controversy regarding the validity of CYP2D6 as a predictor of tamoxifen outcome. Tamoxifen 68-77 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 58-64 26434912-9 2015 However, there was a significant association between CYP2D6 genotype and recurrence in tamoxifen-treated Her2-neu positive patients. Tamoxifen 87-96 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 53-59 26434912-11 2015 CONCLUSIONS: This study for the first time demonstrated significant effects of CYP2D6 extensive metabolizer alleles on risk of recurrence in Her2-neu positive breast cancer patients receiving adjuvant tamoxifen therapy. Tamoxifen 201-210 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 79-85 26434912-12 2015 Therefore, CYP2D6 metabolism, as measured by genetic variation, can be a predictor of breast cancer outcome in Her2-neu positive women receiving tamoxifen. Tamoxifen 145-154 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 11-17 25712191-2 2015 Because CYP2D6 is known to be an important enzyme responsible for the generation of the potent tamoxifen metabolite, "endoxifen", lots of studies reported that genetic variation which reduced its enzyme activity were associated with poor clinical outcome of breast cancer patients treated with tamoxifen. Tamoxifen 95-104 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 8-14 25712191-3 2015 However, there are some discrepant reports questioning the association between CYP2D6 genotype and clinical outcome after tamoxifen therapy. Tamoxifen 122-131 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 79-85 25712191-4 2015 Dose-adjustment study of tamoxifen based on CYP2D6 genotypes provides the evidence that dose adjustment is useful for the patients carrying reduced or null allele of CYP2D6 to maintain the effective endoxifen level. Tamoxifen 25-34 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 44-50 25712191-4 2015 Dose-adjustment study of tamoxifen based on CYP2D6 genotypes provides the evidence that dose adjustment is useful for the patients carrying reduced or null allele of CYP2D6 to maintain the effective endoxifen level. Tamoxifen 25-34 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 166-172 25712191-5 2015 This review describes critical issues in pharmacogenomic studies as well as summarizes the results of the association of CYP2D6 genotype with tamoxifen efficacy. Tamoxifen 142-151 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 121-127 25490892-1 2014 BACKGROUND: Controversy exists regarding the impact of CYP2D6 genotype on tamoxifen responsiveness. Tamoxifen 74-83 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 55-61 26681084-0 2015 Contribution of ABCB1 and CYP2D6 genotypes to the outcome of tamoxifen adjuvant treatment in premenopausal women with breast cancer. Tamoxifen 61-70 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 26-32 24881593-5 2014 The steady-state plasma concentrations of TAM and its active metabolites EDX and 4-hydroxytamoxifen (OHTAM) in patients taking TAM are highly variable, reflecting genetic variants of CYP2D6 involved in TAM metabolism. Tamoxifen 42-45 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 183-189 25073551-0 2014 Simulation with cells in vitro of tamoxifen treatment in premenopausal breast cancer patients with different CYP2D6 genotypes. Tamoxifen 34-43 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 109-115 25073551-1 2014 BACKGROUND AND PURPOSE: Tamoxifen is a prodrug that is metabolically activated by 4-hydroxylation to the potent primary metabolite 4-hydroxytamoxifen (4OHT) or via another primary metabolite N-desmethyltamoxifen (NDMTAM) to a biologically active secondary metabolite endoxifen through a cytochrome P450 2D6 variant system (CYP2D6). Tamoxifen 24-33 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 287-306 25073551-1 2014 BACKGROUND AND PURPOSE: Tamoxifen is a prodrug that is metabolically activated by 4-hydroxylation to the potent primary metabolite 4-hydroxytamoxifen (4OHT) or via another primary metabolite N-desmethyltamoxifen (NDMTAM) to a biologically active secondary metabolite endoxifen through a cytochrome P450 2D6 variant system (CYP2D6). Tamoxifen 24-33 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 323-329 25258390-1 2014 BACKGROUND: Tamoxifen is metabolically activated via a CYP2D6 enzyme system to the more potent hydroxylated derivatives 4-hydroxytamoxifen and endoxifen. Tamoxifen 12-21 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 55-61 25073551-6 2014 The addition of endoxifen at concentrations corresponding to different CYP2D6 genotypes was found to enhance the anti-oestrogenic effect of tamoxifen and its metabolites with an efficacy that correlated with the concentration of endoxifen; at concentrations corresponding to the extensive metabolizer genotype it further inhibited the actions of oestrogen. Tamoxifen 140-149 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 71-77 25318936-1 2014 BACKGROUND: Reduced CYP2D6 metabolism and low Z-endoxifen (ENDX) concentrations may increase the risk of breast cancer recurrence in tamoxifen (TAM)-treated women. Tamoxifen 133-142 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 20-26 25318936-1 2014 BACKGROUND: Reduced CYP2D6 metabolism and low Z-endoxifen (ENDX) concentrations may increase the risk of breast cancer recurrence in tamoxifen (TAM)-treated women. Tamoxifen 144-147 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 20-26 25318936-9 2014 The low 4HT and ENDX concentrations observed in mice receiving s.c. TAM mirror the TAM pharmacokinetics in humans with impaired CYP2D6 metabolism. Tamoxifen 68-71 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 128-134 25296365-1 2014 The CYP2D6 enzyme is crucial for the metabolism of tamoxifen. Tamoxifen 51-60 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 4-10 25296365-2 2014 The CYP2D6 gene is highly polymorphic, and individuals can be extensive, intermediate, or poor tamoxifen metabolizers. Tamoxifen 95-104 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 4-10 25296365-3 2014 The aim of this study was to determine the frequencies of the CYP2D6 *3, *4, and *10 alleles in women with breast cancer who were treated with tamoxifen and analyze the association of enzyme activity with prognostic factors and disease-free survival. Tamoxifen 143-152 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 62-68 24881593-5 2014 The steady-state plasma concentrations of TAM and its active metabolites EDX and 4-hydroxytamoxifen (OHTAM) in patients taking TAM are highly variable, reflecting genetic variants of CYP2D6 involved in TAM metabolism. Tamoxifen 103-106 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 183-189 24881593-5 2014 The steady-state plasma concentrations of TAM and its active metabolites EDX and 4-hydroxytamoxifen (OHTAM) in patients taking TAM are highly variable, reflecting genetic variants of CYP2D6 involved in TAM metabolism. Tamoxifen 103-106 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 183-189 24881593-6 2014 Besides de genetic polymorphisms, the intake of drugs that influence the enzymatic activity of CYP2D6 compromises the therapeutic efficiency of TAM. Tamoxifen 144-147 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 95-101 25114852-0 2014 Impact of CYP2D*6 in the adjuvant treatment of breast cancer patients with tamoxifen. Tamoxifen 75-84 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 10-17 24697814-0 2014 Population pharmacokinetic modelling to assess the impact of CYP2D6 and CYP3A metabolic phenotypes on the pharmacokinetics of tamoxifen and endoxifen. Tamoxifen 126-135 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 61-67 24697814-5 2014 METHODS: We assessed the CYP2D6 and CYP3A metabolic phenotypes in 40 breast cancer patients on tamoxifen treatment with a single dose of dextromethorphan as a dual phenotypic probe for CYP2D6 and CYP3A. Tamoxifen 95-104 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 25-31 24697814-8 2014 In the final model for tamoxifen, the dextromethorphan derived metabolic phenotypes for CYP2D6 as well as CYP3A significantly (P < 0.0001) explained 54% of the observed variability in endoxifen formation (inter-individual variability reduced from 55% to 25%). Tamoxifen 23-32 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 88-94 24697814-9 2014 CONCLUSIONS: We have shown that not only CYP2D6, but also CYP3A enzyme activity influences the tamoxifen to endoxifen conversion in breast cancer patients. Tamoxifen 95-104 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 41-47 24697814-10 2014 Our developed model may be used to assess separately the impact of CYP2D6 and CYP3A mediated drug-drug interactions with tamoxifen without the necessity of administering this anti-oestrogenic drug and to support Bayesian guided therapeutic drug monitoring of tamoxifen in routine clinical practice. Tamoxifen 121-130 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 67-73 25114852-1 2014 Biotransformation of tamoxifen to the potent antiestrogen endoxifen is performed by cytochrome P450 (CYP) enzymes, in particular the CYP2D6 isoform. Tamoxifen 21-30 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 133-139 25114852-7 2014 The present study summarizes current literature regarding clinical studies on CYP2D6*4, particularly in terms of response to tamoxifen therapy and breast cancer outcome. Tamoxifen 125-134 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 78-84 24936398-1 2014 PURPOSE: To overcome cytochrome P450 2D6 (CYP2D6) mediated tamoxifen resistance in postmenopausal early breast cancer, CYP2D6 phenotype-adjusted tamoxifen dosing in patients with impaired CYP2D6 metabolism and/or the application of endoxifen, the most potent tamoxifen metabolite, are alternative treatment options. Tamoxifen 59-68 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 21-40 24685597-0 2014 Adjusting the dose of tamoxifen in patients with early breast cancer and CYP2D6 poor metabolizer phenotype. Tamoxifen 22-31 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 73-79 24685597-1 2014 BACKGROUND: CYP2D6 is a key enzyme in tamoxifen metabolism, transforming it into its main active metabolite, endoxifen. Tamoxifen 38-47 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 12-18 24685597-2 2014 Poor CYP2D6 metabolizers (PM) have lower endoxifen plasma concentrations and possibly benefit less from treatment with tamoxifen. Tamoxifen 119-128 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 5-11 24685597-3 2014 We evaluated tamoxifen dose adjustment in CYP2D6 PM patients in order to obtain plasma concentrations of endoxifen comparable to patients with extensive CYP2D6 metabolism (EM). Tamoxifen 13-22 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 42-48 25056393-0 2014 Interpreting the CYP2D6 results from the International Tamoxifen Pharmacogenetics Consortium. Tamoxifen 55-64 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 17-23 24685597-11 2014 CONCLUSION: In CYP2D6 PM patients, increasing the standard tamoxifen dose two-fold or three-fold raises endoxifen concentrations to levels similar to those of patients with EM phenotype. Tamoxifen 59-68 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 15-21 24747158-4 2014 One hundred and forty patients being treated with tamoxifen were given 30 mg of dextromethorphan and their CYP2D6 phenotypes were determined on the basis of [DMT]/[DTP] metabolic ratios in plasma samples collected after 3h. Tamoxifen 50-59 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 107-113 24936398-1 2014 PURPOSE: To overcome cytochrome P450 2D6 (CYP2D6) mediated tamoxifen resistance in postmenopausal early breast cancer, CYP2D6 phenotype-adjusted tamoxifen dosing in patients with impaired CYP2D6 metabolism and/or the application of endoxifen, the most potent tamoxifen metabolite, are alternative treatment options. Tamoxifen 59-68 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 42-48 24936398-1 2014 PURPOSE: To overcome cytochrome P450 2D6 (CYP2D6) mediated tamoxifen resistance in postmenopausal early breast cancer, CYP2D6 phenotype-adjusted tamoxifen dosing in patients with impaired CYP2D6 metabolism and/or the application of endoxifen, the most potent tamoxifen metabolite, are alternative treatment options. Tamoxifen 59-68 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 119-125 24936398-1 2014 PURPOSE: To overcome cytochrome P450 2D6 (CYP2D6) mediated tamoxifen resistance in postmenopausal early breast cancer, CYP2D6 phenotype-adjusted tamoxifen dosing in patients with impaired CYP2D6 metabolism and/or the application of endoxifen, the most potent tamoxifen metabolite, are alternative treatment options. Tamoxifen 59-68 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 119-125 24936398-1 2014 PURPOSE: To overcome cytochrome P450 2D6 (CYP2D6) mediated tamoxifen resistance in postmenopausal early breast cancer, CYP2D6 phenotype-adjusted tamoxifen dosing in patients with impaired CYP2D6 metabolism and/or the application of endoxifen, the most potent tamoxifen metabolite, are alternative treatment options. Tamoxifen 145-154 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 21-40 24936398-1 2014 PURPOSE: To overcome cytochrome P450 2D6 (CYP2D6) mediated tamoxifen resistance in postmenopausal early breast cancer, CYP2D6 phenotype-adjusted tamoxifen dosing in patients with impaired CYP2D6 metabolism and/or the application of endoxifen, the most potent tamoxifen metabolite, are alternative treatment options. Tamoxifen 145-154 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 42-48 24936398-1 2014 PURPOSE: To overcome cytochrome P450 2D6 (CYP2D6) mediated tamoxifen resistance in postmenopausal early breast cancer, CYP2D6 phenotype-adjusted tamoxifen dosing in patients with impaired CYP2D6 metabolism and/or the application of endoxifen, the most potent tamoxifen metabolite, are alternative treatment options. Tamoxifen 145-154 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 119-125 24936398-1 2014 PURPOSE: To overcome cytochrome P450 2D6 (CYP2D6) mediated tamoxifen resistance in postmenopausal early breast cancer, CYP2D6 phenotype-adjusted tamoxifen dosing in patients with impaired CYP2D6 metabolism and/or the application of endoxifen, the most potent tamoxifen metabolite, are alternative treatment options. Tamoxifen 145-154 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 119-125 24936398-1 2014 PURPOSE: To overcome cytochrome P450 2D6 (CYP2D6) mediated tamoxifen resistance in postmenopausal early breast cancer, CYP2D6 phenotype-adjusted tamoxifen dosing in patients with impaired CYP2D6 metabolism and/or the application of endoxifen, the most potent tamoxifen metabolite, are alternative treatment options. Tamoxifen 145-154 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 21-40 24936398-1 2014 PURPOSE: To overcome cytochrome P450 2D6 (CYP2D6) mediated tamoxifen resistance in postmenopausal early breast cancer, CYP2D6 phenotype-adjusted tamoxifen dosing in patients with impaired CYP2D6 metabolism and/or the application of endoxifen, the most potent tamoxifen metabolite, are alternative treatment options. Tamoxifen 145-154 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 42-48 24936398-1 2014 PURPOSE: To overcome cytochrome P450 2D6 (CYP2D6) mediated tamoxifen resistance in postmenopausal early breast cancer, CYP2D6 phenotype-adjusted tamoxifen dosing in patients with impaired CYP2D6 metabolism and/or the application of endoxifen, the most potent tamoxifen metabolite, are alternative treatment options. Tamoxifen 145-154 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 119-125 24936398-1 2014 PURPOSE: To overcome cytochrome P450 2D6 (CYP2D6) mediated tamoxifen resistance in postmenopausal early breast cancer, CYP2D6 phenotype-adjusted tamoxifen dosing in patients with impaired CYP2D6 metabolism and/or the application of endoxifen, the most potent tamoxifen metabolite, are alternative treatment options. Tamoxifen 145-154 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 119-125 24936398-7 2014 CONCLUSION: In conclusion, we suggest that co-administration of endoxifen in tamoxifen treated early breast cancer women with impaired CYP2D6 metabolism is a promising alternative to reach plasma concentrations comparable to CYP2D6 EM patients. Tamoxifen 77-86 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 135-141 24744093-2 2014 Tamoxifen undergoes hepatic bioactivation by CYP2D6 and CYP3A4 to form the active metabolite endoxifen. Tamoxifen 0-9 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 45-51 24084477-14 2014 Some antidepressants (for example, paroxetine) should be avoided in women concurrently taking tamoxifen due to relevant interactions involving the cytochrome CYP2D6. Tamoxifen 94-103 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 158-164 24033728-0 2014 Prediction of tamoxifen outcome by genetic variation of CYP2D6 in post-menopausal women with early breast cancer. Tamoxifen 14-23 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 56-62 24033728-2 2014 In this article we revisit the hypothesis of CYP2D6 being a potential tamoxifen outcome predictor and provide detailed insight into the ongoing controversy that prevented the CYP2D6 marker from being accepted by the scientific and clinical community. Tamoxifen 70-79 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 45-51 24055701-1 2014 (Z)-Endoxifen (4-hydroxy-N-desmethyltamoxifen), an active metabolite generated via actions of CYP3A4/5 and CYP2D6, is a more potent selective estrogen receptor modulator (SERM) than tamoxifen. Tamoxifen 36-45 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 107-113 24125101-1 2014 BACKGROUND: CYP2D6 is considered the key enzyme in tamoxifen metabolism. Tamoxifen 51-60 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 12-18 24125101-2 2014 Several studies have investigated the relationship between the CYP2D6 genotype and tamoxifen treatment outcome, with discrepant results. Tamoxifen 83-92 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 63-69 24125101-4 2014 We examined the association between CYP2D6 genotype and early breast cancer events in tamoxifen-treated breast cancer patients, in relation to CYP2D6 inhibitor use, aromatase inhibitor use, and chemotherapy. Tamoxifen 86-95 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 36-42 24125101-12 2014 CYP2D6 genotype may be of minor importance for tamoxifen-treated patients in Scandinavia. Tamoxifen 47-56 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 24635399-7 2014 The category tamoxifen+CYP2D6 inhibitor was defined as women who were delivered tamoxifen and a CYP2D6 inhibitor in that subperiod. Tamoxifen 13-22 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 96-102 24635399-7 2014 The category tamoxifen+CYP2D6 inhibitor was defined as women who were delivered tamoxifen and a CYP2D6 inhibitor in that subperiod. Tamoxifen 80-89 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 23-29 24635399-11 2014 DISCUSSION: This study shows that a proportion of women taking tamoxifen in Belgium are prescribed a strong CYP2D6 inhibitor, which could affect tamoxifen efficacy. Tamoxifen 63-72 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 108-114 24635399-11 2014 DISCUSSION: This study shows that a proportion of women taking tamoxifen in Belgium are prescribed a strong CYP2D6 inhibitor, which could affect tamoxifen efficacy. Tamoxifen 145-154 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 108-114 24265036-0 2014 CYP2D6 genotype in relation to hot flashes as tamoxifen side effect in a Dutch cohort of the tamoxifen exemestane adjuvant multinational (TEAM) trial. Tamoxifen 46-55 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 24265036-3 2014 CYP2D6 genotypes and phenotypes were related to the occurrence of hot flashes as adverse event during the first year of tamoxifen use (primary aim) and the time to the occurrence of hot flashes as AE during the complete time on tamoxifen (secondary aim). Tamoxifen 120-129 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 24265036-3 2014 CYP2D6 genotypes and phenotypes were related to the occurrence of hot flashes as adverse event during the first year of tamoxifen use (primary aim) and the time to the occurrence of hot flashes as AE during the complete time on tamoxifen (secondary aim). Tamoxifen 228-237 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 24434530-2 2014 Tamoxifen is a mainly inactive prodrug, necessitating metabolism by the cytochrome P450 (CYP450) pathway, predominantly the Cytochrome P450 2D6 (CYP2D6), into the active metabolites 4-hydroxytamoxifen and, in particular, endoxifen to achieve its therapeutic effect. Tamoxifen 0-9 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 124-143 24434530-2 2014 Tamoxifen is a mainly inactive prodrug, necessitating metabolism by the cytochrome P450 (CYP450) pathway, predominantly the Cytochrome P450 2D6 (CYP2D6), into the active metabolites 4-hydroxytamoxifen and, in particular, endoxifen to achieve its therapeutic effect. Tamoxifen 0-9 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 145-151 24434530-3 2014 As several women treated with tamoxifen may experience depressive symptoms or may have a previous or actual major depressive episode with ongoing antidepressant treatment or need for a new-onset therapy, the coprescription of an antidepressant drug may be particularly problematic as several antidepressants are potent CYP2D6-inhibiting drugs. Tamoxifen 30-39 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 319-325 24060820-1 2014 The International Tamoxifen Pharmacogenomics Consortium was established to address the controversy regarding cytochrome P450 2D6 (CYP2D6) status and clinical outcomes in tamoxifen therapy. Tamoxifen 18-27 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 109-128 24060820-1 2014 The International Tamoxifen Pharmacogenomics Consortium was established to address the controversy regarding cytochrome P450 2D6 (CYP2D6) status and clinical outcomes in tamoxifen therapy. Tamoxifen 18-27 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 130-136 24060820-3 2014 Using strict eligibility requirements (postmenopausal women with estrogen receptor-positive breast cancer, receiving 20 mg/day tamoxifen for 5 years, criterion 1); CYP2D6 poor metabolizer status was associated with poorer invasive disease-free survival (IDFS: hazard ratio = 1.25; 95% confidence interval = 1.06, 1.47; P = 0.009). Tamoxifen 127-136 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 164-170 24635399-0 2014 How often did Belgian physicians co-prescribe tamoxifen with strong CYP2D6 inhibitors over the last 6 years? Tamoxifen 46-55 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 68-74 24265353-0 2014 The rs1800716 variant in CYP2D6 is associated with an increased double endometrial thickness in postmenopausal women on tamoxifen. Tamoxifen 120-129 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 25-31 24328412-2 2014 Tamoxifen is metabolized to more active metabolites by enzymes encoded by polymorphic genes, including cytochrome P450 2D6 (CYP2D6). Tamoxifen 0-9 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 103-122 24328412-2 2014 Tamoxifen is metabolized to more active metabolites by enzymes encoded by polymorphic genes, including cytochrome P450 2D6 (CYP2D6). Tamoxifen 0-9 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 124-130 24328412-4 2014 We review tamoxifen"s clinical pharmacology and use meta-analyses to evaluate the clinical epidemiology studies conducted to date on the association between CYP2D6 inhibition and tamoxifen effectiveness. Tamoxifen 179-188 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 157-163 24368234-0 2014 Response to "Understanding CYP2D6 and its role in tamoxifen metabolism" Tamoxifen 50-59 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 27-33 25378122-1 2014 BACKGROUND: Several previous studies have examined the effect of CYP2D6 gene polymorphism on the efficacy and metabolism of tamoxifen (Tamoxifen Teva, Nolvadex) in the treatment of breast cancer. Tamoxifen 124-133 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 65-71 24329190-0 2014 Association between CYP2D6 genotypes and the clinical outcomes of adjuvant tamoxifen for breast cancer: a meta-analysis. Tamoxifen 75-84 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 20-26 24329190-3 2014 This study evaluated the association between CYP2D6 genotypes and postoperative tamoxifen treatment outcome in patients with breast cancer, using the available previous study results. Tamoxifen 80-89 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 45-51 24329190-4 2014 MATERIALS & METHODS: We performed a meta-analysis of ten previous clinical reports (n = 5183) to evaluate the association between CYP2D6 genotype and hazard ratios for the recurrence risk of breast cancer after postoperative tamoxifen treatment. Tamoxifen 229-238 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 134-140 24329190-9 2014 CONCLUSION: Our present findings suggest that genetic polymorphisms of CYP2D6 may be important predictors of the clinical outcomes of adjuvant tamoxifen treatment for the patients with breast cancer. Tamoxifen 143-152 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 71-77 25378122-1 2014 BACKGROUND: Several previous studies have examined the effect of CYP2D6 gene polymorphism on the efficacy and metabolism of tamoxifen (Tamoxifen Teva, Nolvadex) in the treatment of breast cancer. Tamoxifen 151-159 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 65-71 24730084-0 2014 CYP2D6 pharmacogenomics of tamoxifen treatment. Tamoxifen 27-36 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 24457521-1 2014 BACKGROUND: CYP2D6 is a critical enzyme in the metabolism of tamoxifen and potentially a key determinant in breast cancer outcomes. Tamoxifen 61-70 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 12-18 23893861-0 2013 Pharmacogenetic testing in the face of unclear clinical efficacy: lessons from cytochrome P450 2D6 for tamoxifen. Tamoxifen 103-112 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 79-98 23881421-12 2013 The results of this clinical study indicate that GSE appears to be safe to combine with drugs extensively metabolized by CYP2D6, such as dextromethorphan and tamoxifen. Tamoxifen 158-167 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 121-127 24161632-0 2013 Understanding CYP2D6 and its role in tamoxifen metabolism. Tamoxifen 37-46 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 14-20 23893861-1 2013 BACKGROUND: This study evaluated self-reported knowledge, practice, and attitudes toward commercially available cytochrome P450 2D6 (CYP2D6) pharmacogenomic testing for patients on tamoxifen for breast cancer (CYPT) among US oncologists while evidence for the use of the test was evolving. Tamoxifen 181-190 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 112-131 23893861-1 2013 BACKGROUND: This study evaluated self-reported knowledge, practice, and attitudes toward commercially available cytochrome P450 2D6 (CYP2D6) pharmacogenomic testing for patients on tamoxifen for breast cancer (CYPT) among US oncologists while evidence for the use of the test was evolving. Tamoxifen 181-190 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 133-139 24098545-1 2013 OBJECTIVE: To evaluate evidence on the association between CYP2D6 genotype and tamoxifen response through. Tamoxifen 79-88 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 59-65 23958736-2 2013 The anti-estrogen tamoxifen is metabolized into endoxifen by CYP2D6, leading to the hypothesis that patients with certain CYP2D6 genotypes may not receive benefit because of their inability to activate the drug. Tamoxifen 18-27 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 61-67 24098545-8 2013 Three randomized trials evaluated the effect of CYP2D6 genotype on tamoxifen response ("effect modification" design). Tamoxifen 67-76 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 48-54 24098545-11 2013 From two randomized trials that permitted effect-modification analysis, one had only 154 patients and showed evidence of effect modification of tamoxifen by CYP2D6 genotype for distant recurrence but was directionally opposite to that predicted, whereas a larger trial of 2,537 patients failed to show evidence of effect modification for breast cancer-free interval (P values for interaction 0.02 and 0.44, respectively). Tamoxifen 144-153 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 157-163 24062210-2 2013 Genotypic variation in CYP2D6 affects endoxifen levels, and some have argued that patients who do not efficiently metabolize tamoxifen might wish to consider alternative hormonal treatments. Tamoxifen 125-134 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 23-29 24062210-13 2013 Prospective testing of tamoxifen metabolism as gauged by CYP2D6 genotype and serum endoxifen levels is feasible. Tamoxifen 23-32 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 57-63 24088129-2 2013 We determined the frequency of polymorphisms in the CYP2D6 gene associated with activation of tamoxifen, and those of the genes CYP2C8, CYP3A5 and DPYD associated with toxicity of paclitaxel and capecitabine. Tamoxifen 94-103 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 52-58 23958736-2 2013 The anti-estrogen tamoxifen is metabolized into endoxifen by CYP2D6, leading to the hypothesis that patients with certain CYP2D6 genotypes may not receive benefit because of their inability to activate the drug. Tamoxifen 18-27 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 122-128 23711794-5 2013 The pharmacological activity of Tamoxifen is dependent on its conversion to its active metabolite, endoxifen, by CYP2D6. Tamoxifen 32-41 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 113-119 23996142-15 2013 This may represent an additional explanation why studies on the effects of CYP2D6 polymorphisms on outcome in tamoxifen-treated breast cancer patients have been inconsistent. Tamoxifen 110-119 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 75-81 29776195-1 2013 A case study of CYP2D6 testing in the treatment of breast cancer with tamoxifen. Tamoxifen 70-79 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 16-22 24648760-0 2013 Effects of CYP2D6 and UGT2B7 polymorphisms on pharmacokinetics of tamoxifen in Thai breast cancer patients. Tamoxifen 66-75 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 11-17 24648760-1 2013 PURPOSE: The objective of this study was to evaluate the impact of CYP2D6 and UGT2B7 polymorphisms on tamoxifen (TAM) pharmacokinetics in Thai breast cancer patients. Tamoxifen 102-111 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 67-73 24648760-1 2013 PURPOSE: The objective of this study was to evaluate the impact of CYP2D6 and UGT2B7 polymorphisms on tamoxifen (TAM) pharmacokinetics in Thai breast cancer patients. Tamoxifen 113-116 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 67-73 24648760-10 2013 CONCLUSION: Results from this study confirmed the impacts of CYP2D6 polymorphisms on the pharmacokinetics of TAM, while UGT2B7 polymorphisms tended to have impact on TAM metabolism in patients with homozygous CYP2D6*10. Tamoxifen 109-112 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 61-67 24648760-10 2013 CONCLUSION: Results from this study confirmed the impacts of CYP2D6 polymorphisms on the pharmacokinetics of TAM, while UGT2B7 polymorphisms tended to have impact on TAM metabolism in patients with homozygous CYP2D6*10. Tamoxifen 166-169 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 209-215 24019753-2 2013 Apart from CYP2D6, other drug-metabolizing enzymes and transporters also play a role in tamoxifen metabolic pathways. Tamoxifen 88-97 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 11-17 23712329-0 2013 CYP2D6 polymorphisms influence tamoxifen treatment outcomes in breast cancer patients: a meta-analysis. Tamoxifen 31-40 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 23712329-11 2013 CONCLUSIONS: We concluded that CYP2D6 polymorphisms may influence tamoxifen treatment outcomes of DFS in BC patients. Tamoxifen 66-75 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 31-37 29776195-2 2013 This paper reports the process and experience of the design and conduct of a UK-based health technology assessment (HTA) of CYP2D6 pharmacogenetic testing to inform the targeted use of tamoxifen for the treatment of breast cancer. Tamoxifen 185-194 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 124-130 23836010-1 2013 To date, three molecular markers (ER, PR, and CYP2D6) have been used in clinical setting to predict the benefit of the anti-estrogen tamoxifen therapy. Tamoxifen 133-142 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 46-52 23922954-3 2013 In this descriptive study, correlations were examined between concentrations of tamoxifen metabolites and genotypes for CYP2D6, CYP3A4, CYP3A5, SULT1A1, SULT1A2 and SULT1E1 in 135 patients with estrogen receptor-positive breast cancer. Tamoxifen 80-89 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 120-126 23922954-9 2013 Our observations indicate that besides the CYP2D6 genotype leading to tamoxifen conversion to potent hydroxylated metabolites in a manner consistent with a gene-dose effect, SULT1A2 also seems to play a role in maintaining optimal levels of both 4-hydroxy-tamoxifen and endoxifen. Tamoxifen 70-79 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 43-49 23842856-0 2013 CYP2D6 genotype in relation to tamoxifen efficacy in a Dutch cohort of the tamoxifen exemestane adjuvant multinational (TEAM) trial. Tamoxifen 31-40 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 23842856-1 2013 The clinical importance of CYP2D6 genotype as predictor of tamoxifen efficacy is still unclear. Tamoxifen 59-68 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 27-33 23842856-4 2013 CYP2D6 genotypes and phenotypes were related to disease-free survival during tamoxifen use (DFS-t) in 731 patients. Tamoxifen 77-86 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 23786776-13 2013 Within the tamoxifen arm, CYP2D6 polymorphism analysis showed a higher concentration of N-desTamoxifen, one of the tamoxifen metabolites, in subjects with reduced CYP2D6 activity. Tamoxifen 11-20 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 26-32 23786776-13 2013 Within the tamoxifen arm, CYP2D6 polymorphism analysis showed a higher concentration of N-desTamoxifen, one of the tamoxifen metabolites, in subjects with reduced CYP2D6 activity. Tamoxifen 11-20 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 163-169 23786776-13 2013 Within the tamoxifen arm, CYP2D6 polymorphism analysis showed a higher concentration of N-desTamoxifen, one of the tamoxifen metabolites, in subjects with reduced CYP2D6 activity. Tamoxifen 115-124 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 26-32 23786776-16 2013 However, in the tamoxifen arm women with an extensive phenotype for CYP2D6 reached a significant Ki-67 modulation. Tamoxifen 16-25 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 68-74 23781139-0 2013 Influence of CYP2D6 polymorphisms on serum levels of tamoxifen metabolites in Spanish women with breast cancer. Tamoxifen 53-62 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 13-19 23604525-6 2013 Clomiphene, tamoxifen and toremifene were biotransformed to 22, 23 and 18 metabolites respectively, these phase I reactions being catalyzed mainly by CYP3A4 and CYP2D6 isoforms and, to a lesser degree, by CYP3A5, CYP2B6, CYP2C9, CYP2C19 isoforms. Tamoxifen 12-21 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 161-167 23760858-0 2013 Unjustified prescribing of CYP2D6 inhibiting SSRIs in women treated with tamoxifen. Tamoxifen 73-82 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 27-33 23760858-2 2013 Since the cytochrome P450 (CYP) 2D6 enzyme is primarily involved in this metabolism, genetic polymorphisms of this enzyme, but also drug-induced CYP2D6 inhibition can result in considerably reduced endoxifen formation and as a consequence may affect the efficacy of tamoxifen treatment. Tamoxifen 266-275 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 10-35 23760858-2 2013 Since the cytochrome P450 (CYP) 2D6 enzyme is primarily involved in this metabolism, genetic polymorphisms of this enzyme, but also drug-induced CYP2D6 inhibition can result in considerably reduced endoxifen formation and as a consequence may affect the efficacy of tamoxifen treatment. Tamoxifen 266-275 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 145-151 23760858-5 2013 Evidence of a significant influence of strong CYP2D6-inhibiting drugs on the pharmacokinetics of tamoxifen has resulted in recommendations to avoid potent CYP2D6-inhibiting antidepressants (e.g., paroxetine, fluoxetine) in patients treated with tamoxifen for breast cancer. Tamoxifen 97-106 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 46-52 23760858-5 2013 Evidence of a significant influence of strong CYP2D6-inhibiting drugs on the pharmacokinetics of tamoxifen has resulted in recommendations to avoid potent CYP2D6-inhibiting antidepressants (e.g., paroxetine, fluoxetine) in patients treated with tamoxifen for breast cancer. Tamoxifen 97-106 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 155-161 23760858-5 2013 Evidence of a significant influence of strong CYP2D6-inhibiting drugs on the pharmacokinetics of tamoxifen has resulted in recommendations to avoid potent CYP2D6-inhibiting antidepressants (e.g., paroxetine, fluoxetine) in patients treated with tamoxifen for breast cancer. Tamoxifen 245-254 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 46-52 23760858-6 2013 Nevertheless, dispensing data for tamoxifen and seven regularly used SSRIs/SNRIs in the period between 2005 and 2010, obtained from a large community pharmacy database in the Netherlands (3,000,000 people), show that the potent CYP2D6-inhibiting drug paroxetine remains one of the most frequently used antidepressants in tamoxifen-treated patients. Tamoxifen 34-43 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 228-234 23760858-6 2013 Nevertheless, dispensing data for tamoxifen and seven regularly used SSRIs/SNRIs in the period between 2005 and 2010, obtained from a large community pharmacy database in the Netherlands (3,000,000 people), show that the potent CYP2D6-inhibiting drug paroxetine remains one of the most frequently used antidepressants in tamoxifen-treated patients. Tamoxifen 321-330 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 228-234 23760858-11 2013 In clinical practice, one should strive to avoid potent CYP2D6 inhibitors as much as possible in tamoxifen-treated patients to reduce the risk of compromising the efficacy of the hormonal therapy. Tamoxifen 97-106 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 56-62 23657426-3 2013 Among these enzymes, CYP2D6 is considered to be a rate-limiting enzyme in the generation of endoxifen, a principal active metabolite of tamoxifen, and the genetic polymorphisms of CYP2D6 have been extensively investigated in association with the plasma endoxifen concentrations and clinical outcome of tamoxifen therapy. Tamoxifen 136-145 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 21-27 23657426-3 2013 Among these enzymes, CYP2D6 is considered to be a rate-limiting enzyme in the generation of endoxifen, a principal active metabolite of tamoxifen, and the genetic polymorphisms of CYP2D6 have been extensively investigated in association with the plasma endoxifen concentrations and clinical outcome of tamoxifen therapy. Tamoxifen 136-145 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 180-186 23657426-3 2013 Among these enzymes, CYP2D6 is considered to be a rate-limiting enzyme in the generation of endoxifen, a principal active metabolite of tamoxifen, and the genetic polymorphisms of CYP2D6 have been extensively investigated in association with the plasma endoxifen concentrations and clinical outcome of tamoxifen therapy. Tamoxifen 302-311 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 21-27 23657426-3 2013 Among these enzymes, CYP2D6 is considered to be a rate-limiting enzyme in the generation of endoxifen, a principal active metabolite of tamoxifen, and the genetic polymorphisms of CYP2D6 have been extensively investigated in association with the plasma endoxifen concentrations and clinical outcome of tamoxifen therapy. Tamoxifen 302-311 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 180-186 23657426-4 2013 In addition to CYP2D6, other genetic factors including polymorphisms in various drug-metabolizing enzymes and drug transporters have been implicated to their relations to clinical outcome of tamoxifen therapy, but their effects would be small. Tamoxifen 191-200 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 15-21 23588782-4 2013 CYP2D6 is responsible for the oxidative metabolism of up to 25% of commonly prescribed drugs such as antidepressants, antipsychotics, opioids, antiarrythmics and tamoxifen. Tamoxifen 162-171 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 23588782-9 2013 Although conflicting results have been reported regarding the association between CYP2D6 genotype and tamoxifen effects, CYP2D6 genotyping may be useful in selecting adjuvant hormonal therapy in postmenopausal women. Tamoxifen 102-111 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 82-88 23686417-0 2013 Influence of CYP2D6-genotype on tamoxifen efficacy in advanced breast cancer. Tamoxifen 32-41 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 13-19 23686417-1 2013 The influence of CYP2D6 genotype on the efficacy of tamoxifen (Tam) has been extensively analyzed in early breast cancer with conflicting results. Tamoxifen 52-61 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 17-23 23686417-1 2013 The influence of CYP2D6 genotype on the efficacy of tamoxifen (Tam) has been extensively analyzed in early breast cancer with conflicting results. Tamoxifen 63-66 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 17-23 23686417-3 2013 We hypothesize that Tam is more effective in patients with a functional CYP2D6 allele than in patients with impaired CYP2D6 activity. Tamoxifen 20-23 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 72-78 23686417-15 2013 Our results show a significant influence of the CYP2D6 genotype on the efficacy of Tam in the treatment of ABC. Tamoxifen 83-86 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 48-54 23781139-2 2013 Polymorphisms of the CYP2D6 and CYP2C19 genes are associated with an impaired response to tamoxifen. Tamoxifen 90-99 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 21-27 23781139-3 2013 The study objective was to investigate the impact of genetic polymorphisms in CYP2D6 and CYP2C19 on the pharmacokinetics of tamoxifen and its metabolites in Spanish women with estrogen receptor-positive breast cancer who were candidates for tamoxifen therapy. Tamoxifen 124-133 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 78-84 23776391-0 2013 Association of CYP2D6 and CYP2C19 polymorphisms and disease-free survival of Thai post-menopausal breast cancer patients who received adjuvant tamoxifen. Tamoxifen 143-152 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 15-21 23605084-2 2013 Tamoxifen is known to undergo CYP2D6-mediated bioactivation to the active metabolite endoxifen. Tamoxifen 0-9 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 30-36 23776391-1 2013 PURPOSE: To investigate the impact of CYP2D6 and CYP2C19 polymorphisms in predicting tamoxifen efficacy and clinical outcomes in Thai breast cancer patients. Tamoxifen 85-94 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 38-44 23776391-8 2013 However, in the subgroup of post-menopausal women, the polymorphisms in CYP2D6 and CYP2C19 might be useful in predicting tamoxifen efficacy and clinical outcomes in breast cancer patients receiving adjuvant tamoxifen treatment. Tamoxifen 121-130 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 72-78 23776391-8 2013 However, in the subgroup of post-menopausal women, the polymorphisms in CYP2D6 and CYP2C19 might be useful in predicting tamoxifen efficacy and clinical outcomes in breast cancer patients receiving adjuvant tamoxifen treatment. Tamoxifen 207-216 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 72-78 23580071-0 2013 CYP3A4 and seasonal variation in vitamin D status in addition to CYP2D6 contribute to therapeutic endoxifen level during tamoxifen therapy. Tamoxifen 121-130 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 65-71 23570463-0 2013 Highlights from the latest articles in CYP2D6 activity and breast cancer outcomes during treatment with tamoxifen. Tamoxifen 104-113 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 39-45 23580071-1 2013 Tamoxifen is a widely utilized adjuvant anti-estrogen agent for hormone receptor-positive breast cancer, known to undergo CYP2D6-mediated bioactivation to endoxifen. Tamoxifen 0-9 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 122-128 23538253-3 2013 This article reviews the pharmacology of tamoxifen, the genetics and physiology of the CYP2D6 enzyme system that has important effects on tamoxifen metabolism, and subset data analyses from large controlled, clinical trials that cast new light on previously held beliefs about the utility of CYP2D6 genotyping for predicting tamoxifen effectiveness and improved breast cancer outcomes in women with early-stage, hormone receptor-positive breast cancer. Tamoxifen 138-147 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 87-93 23538253-3 2013 This article reviews the pharmacology of tamoxifen, the genetics and physiology of the CYP2D6 enzyme system that has important effects on tamoxifen metabolism, and subset data analyses from large controlled, clinical trials that cast new light on previously held beliefs about the utility of CYP2D6 genotyping for predicting tamoxifen effectiveness and improved breast cancer outcomes in women with early-stage, hormone receptor-positive breast cancer. Tamoxifen 138-147 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 87-93 23671949-0 2013 CYP2D6 genotype predicts tamoxifen side effects but not cancer-free or survival benefits in postmenopausal ER+ and/or PgR+ breast cancers. Tamoxifen 25-34 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 23638818-5 2013 In this review, the authors will discuss the current evidence on the most important metabolizing enzymes in endocrine therapy, with a special focus on CYP2D6 and its role in tamoxifen metabolism. Tamoxifen 174-183 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 151-157 23570465-2 2013 We analyzed the impact of the CYP2D6 polymorphism in pre- and post-menopausal patients that were adherent to tamoxifen treatment for at least a year. Tamoxifen 109-118 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 30-36 23570465-6 2013 RESULTS & CONCLUSION: In patients adherent to tamoxifen for at least one year (n = 313) there was an association between reduced CYP2D6 activity (<=50% of normal) and recurrence (p = 0.025) and breast cancer-specific mortality (p = 0.034). Tamoxifen 50-59 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 133-139 23228987-2 2013 CYP2D6 is the main enzyme involved in the activation of the prodrug tamoxifen into the anti-estrogen endoxifen. Tamoxifen 68-77 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 22915089-0 2013 Role and pharmacologic significance of cytochrome P-450 2D6 in oxidative metabolism of toremifene and tamoxifen. Tamoxifen 102-111 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 39-59 22915089-3 2013 Unlike TOR, TAM and its NDM metabolite were extensively oxidized to 4-OH TAM and 4-OH-NDM TAM by CYP2D6, and the rate of metabolism was affected by CYP2D6 status. Tamoxifen 12-15 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 97-103 22915089-3 2013 Unlike TOR, TAM and its NDM metabolite were extensively oxidized to 4-OH TAM and 4-OH-NDM TAM by CYP2D6, and the rate of metabolism was affected by CYP2D6 status. Tamoxifen 12-15 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 148-154 22915089-7 2013 Our findings suggest that variations in CYP2D6 metabolic capacity may cause significant differences in plasma concentrations of active TAM metabolites (i.e., 4-OH TAM and 4-OH-NDM TAM) and contribute to variable pharmacologic activity. Tamoxifen 135-138 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 40-46 23100173-3 2013 Here, we conducted a matched cohort study to determine the impact of an extensive CYP2D6 phenotype on relapse in patients with early-stage estrogen receptor (ER)-positive BC and adjuvant tamoxifen intake. Tamoxifen 187-196 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 82-88 23100173-10 2013 CONCLUSIONS: This study suggests a positive association between extensive CYP2D6 metabolism and outcome in early-stage ER-positive BC patients using tamoxifen and in particular, when a sufficient number ERs are represented on the primary tumor. Tamoxifen 149-158 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 74-80 23091108-0 2013 Tamoxifen use in postmenopausal breast cancer: CYP2D6 matters. Tamoxifen 0-9 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 47-53 23089672-7 2013 Furthermore, the analgesic and side effects of codeine in relation to CYP2D6 polymorphism are supported and the influence of CYP2D6 genotype on breast cancer recurrence during tamoxifen treatment appears relevant as based on three large studies. Tamoxifen 176-185 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 125-131 23346096-3 2012 The recognition that functional CYP2D6 polymorphisms affect tamoxifen pharmacokinetics has motivated the attempts of using CYP2D6 genotyping for predicting breast cancer outcomes. Tamoxifen 60-69 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 32-38 23346096-8 2012 The data indicate that, although CYP2D6 polymorphisms can indeed modify tamoxifen pharmacokinetics, CYP2D6 genotyping alone is not enough for predicting breast cancer outcomes. Tamoxifen 72-81 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 33-39 23213055-9 2013 CONCLUSION: In ABCSG8, the negative effects of reduced CYP2D6 metabolism were observed only during the period of tamoxifen administration and not after switching to anastrozole. Tamoxifen 113-122 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 55-61 23149465-1 2013 Nearly a decade ago, researchers identified a potential interaction between tamoxifen and strong CYP2D6 inhibitors, including several frequently used antidepressants. Tamoxifen 76-85 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 97-103 23149465-2 2013 Based on evidence available at that time, a United States Food and Drug Administration advisory committee recommended tamoxifen"s label be changed in October 2006, noting that postmenopausal women with estrogen receptor-positive breast cancer who are poor CYP2D6 metabolizers by genotype or drug interactions may be at increased risk of cancer recurrence. Tamoxifen 118-127 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 256-262 23149465-12 2013 In conclusion, there were substantial declines in strong CYP2D6-inhibitor use among tamoxifen users following dissemination of information suggesting a potential for increased risk with co-prescribing. Tamoxifen 84-93 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 57-63 23233861-7 2012 Of the proposed gene/drug pairs the highest importance was assigned to HLA-B/abacavir, UGT1A1/irinotecan, and CYP2D6/tamoxifen. Tamoxifen 117-126 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 110-116 22955113-0 2012 Laboratory testing of CYP2D6 alleles in relation to tamoxifen therapy. Tamoxifen 52-61 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 22-28 22955113-1 2012 Tamoxifen, a widely prescribed drug for the treatment and prevention of breast cancer, is metabolized to more potent metabolites by the cytochrome P450 2D6 (CYP2D6) enzyme. Tamoxifen 0-9 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 136-155 22955113-1 2012 Tamoxifen, a widely prescribed drug for the treatment and prevention of breast cancer, is metabolized to more potent metabolites by the cytochrome P450 2D6 (CYP2D6) enzyme. Tamoxifen 0-9 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 157-163 22955113-2 2012 Variants in the CYP2D6 gene can cause patients to be either intermediate or poor metabolizers, thereby rendering tamoxifen treatment less effective. Tamoxifen 113-122 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 16-22 24088226-0 2013 Association of CYP2D6 metabolizer status with mammographic density change in response to tamoxifen treatment. Tamoxifen 89-98 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 15-21 24088226-2 2013 As tamoxifen-induced reductions in percent mammographic density (PMD) have been linked to the risk and prognosis of breast cancer, we conducted a candidate gene study to investigate the association between germline CYP2D6 polymorphisms and PMD change. Tamoxifen 3-12 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 215-221 24088226-3 2013 METHODS: Baseline and follow-up mammograms were retrieved for 278 tamoxifen-treated subjects with CYP2D6 metabolizer status (extensive (EM), heterozygous extensive/intermediate (hetEM/IM) or poor metabolizer (PM)). Tamoxifen 66-75 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 98-104 23565321-3 2013 Genetic variants in CYP2D6 and other drug-metabolizing enzymes that alter the metabolism of tamoxifen may be associated with CBC risk in women who receive the drug. Tamoxifen 92-101 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 20-26 22638694-2 2012 Variation in the CYP2D6 gene and concomitant use of tamoxifen (TAM) with certain antidepressants may increase recurrence risk in breast cancer patients due to reduced enzyme activity. Tamoxifen 52-61 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 17-23 22723326-6 2012 Findings were correlated with CYP2D6 genotype because of CYP2D6 polymorphism associations with tamoxifen-induced hot flashes. Tamoxifen 95-104 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 30-36 22723326-6 2012 Findings were correlated with CYP2D6 genotype because of CYP2D6 polymorphism associations with tamoxifen-induced hot flashes. Tamoxifen 95-104 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 57-63 22688624-0 2012 Impact of CYP2D6 polymorphism on tamoxifen therapy: where are we? Tamoxifen 33-42 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 10-16 22777153-1 2012 BACKGROUND: An association between CYP2D6 variation and clinical outcomes among women with breast cancer treated with tamoxifen (TAM) has been demonstrated, such that the presence of 2 functional CYP2D6 alleles was associated with better clinical outcomes. Tamoxifen 118-127 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 35-41 22777153-1 2012 BACKGROUND: An association between CYP2D6 variation and clinical outcomes among women with breast cancer treated with tamoxifen (TAM) has been demonstrated, such that the presence of 2 functional CYP2D6 alleles was associated with better clinical outcomes. Tamoxifen 118-127 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 196-202 22777153-1 2012 BACKGROUND: An association between CYP2D6 variation and clinical outcomes among women with breast cancer treated with tamoxifen (TAM) has been demonstrated, such that the presence of 2 functional CYP2D6 alleles was associated with better clinical outcomes. Tamoxifen 129-132 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 35-41 22777153-1 2012 BACKGROUND: An association between CYP2D6 variation and clinical outcomes among women with breast cancer treated with tamoxifen (TAM) has been demonstrated, such that the presence of 2 functional CYP2D6 alleles was associated with better clinical outcomes. Tamoxifen 129-132 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 196-202 22777153-2 2012 This association is mainly due to the CYP2D6-mediated hydroxylation of N-desmethyltamoxifen (NDT) to yield endoxifen (EDF), which because of its high antiestrogenic potency, is mainly responsible for the therapeutic efficacy of TAM. Tamoxifen 228-231 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 38-44 22676198-1 2012 CYP2D6 is genotyped clinically for prediction of response to tamoxifen, psychotropic drugs and other medications. Tamoxifen 61-70 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 21917382-3 2012 Cytochrome P450 isoform 2D6 (CYP2D6) is a key step in the metabolism of tamoxifen to its active moiety endoxifen. Tamoxifen 72-81 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-27 21917382-3 2012 Cytochrome P450 isoform 2D6 (CYP2D6) is a key step in the metabolism of tamoxifen to its active moiety endoxifen. Tamoxifen 72-81 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 29-35 21917382-4 2012 Women with functionally deficient genetic variants of CYP2D6 who are given drugs that inhibit CYP2D6 are exposed to low endoxifen plasma levels and may enjoy reduced benefits from tamoxifen treatment. Tamoxifen 180-189 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 54-60 21917382-4 2012 Women with functionally deficient genetic variants of CYP2D6 who are given drugs that inhibit CYP2D6 are exposed to low endoxifen plasma levels and may enjoy reduced benefits from tamoxifen treatment. Tamoxifen 180-189 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 94-100 21917382-5 2012 Therefore, CYP2D6 status may be an important predictor of the benefits of tamoxifen to an individual; unfortunately, the data are not uniformly concordant, and definitive evidence that would suggest the routine analysis of CYP2D6 before commencing tamoxifen treatment is not yet available. Tamoxifen 74-83 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 11-17 22735900-1 2012 BACKGROUND: Several studies have reported discordant results regarding the impact of the CYP2D6 phenotype on both the effectiveness and the degree of endocrine symptoms associated with tamoxifen. Tamoxifen 185-194 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 89-95 22735900-3 2012 METHODS: We investigated the relationship between the CYP2D6-predicted phenotype and tamoxifen response in a nested case-control study among women from the International Breast cancer Intervention Study (IBIS-I), which evaluated tamoxifen in the preventive setting. Tamoxifen 85-94 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 54-60 22735900-3 2012 METHODS: We investigated the relationship between the CYP2D6-predicted phenotype and tamoxifen response in a nested case-control study among women from the International Breast cancer Intervention Study (IBIS-I), which evaluated tamoxifen in the preventive setting. Tamoxifen 229-238 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 54-60 22623212-0 2012 Genetic polymorphisms of CYP2D6 increase the risk for recurrence of breast cancer in patients receiving tamoxifen as an adjuvant therapy. Tamoxifen 104-113 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 25-31 22623212-3 2012 This study was conducted to evaluate the influence of CYP2D6 genetic polymorphisms on the recurrence of breast cancer in patients receiving treatment with tamoxifen as an adjuvant hormonal therapy. Tamoxifen 155-164 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 54-60 22623212-14 2012 CONCLUSION: Reduced CYP2D6 activity is associated with poor treatment outcomes, in terms of increased risk of recurrence and shorter recurrence free survival, in breast cancer patients on adjuvant tamoxifen therapy. Tamoxifen 197-206 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 20-26 22294487-0 2012 Estimation of tamoxifen metabolite concentrations in the blood of breast cancer patients through CYP2D6 genotype activity score. Tamoxifen 14-23 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 97-103 22294487-1 2012 Tamoxifen, a prodrug used for adjuvant breast cancer therapy, requires conversion to the active metabolite endoxifen through CYP 2D6. Tamoxifen 0-9 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 125-132 23864928-6 2012 Our study suggests that boron-based 4-hydroxytamoxifen bioisosteres may be an effective therapeutic remedy for intrinsic tamoxifen resistance in breast cancer patients deficient in CYP2D6 metabolism. Tamoxifen 45-54 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 181-187 22661948-0 2012 Physiologically Based Pharmacokinetic Modeling of Tamoxifen and its Metabolites in Women of Different CYP2D6 Phenotypes Provides New Insight into the Tamoxifen Mass Balance. Tamoxifen 50-59 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 102-108 22661948-0 2012 Physiologically Based Pharmacokinetic Modeling of Tamoxifen and its Metabolites in Women of Different CYP2D6 Phenotypes Provides New Insight into the Tamoxifen Mass Balance. Tamoxifen 150-159 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 102-108 22661948-2 2012 Endoxifen is a secondary and highly active metabolite of tamoxifen that is formed among others by the polymorphic cytochrome P450 2D6 (CYP2D6). Tamoxifen 57-66 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 114-133 22661948-2 2012 Endoxifen is a secondary and highly active metabolite of tamoxifen that is formed among others by the polymorphic cytochrome P450 2D6 (CYP2D6). Tamoxifen 57-66 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 135-141 22661948-4 2012 Nevertheless, an in-depth understanding of the chain of cause and effect between CYP2D6 genotype, endoxifen steady-state plasma concentration, and subsequent tamoxifen treatment benefit still remains to be evolved. Tamoxifen 158-167 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 81-87 22661948-5 2012 In this study, physiologically based pharmacokinetic (PBPK)-modeling was applied to mechanistically investigate the impact of CYP2D6 phenotype on endoxifen formation in female breast cancer patients undergoing tamoxifen therapy. Tamoxifen 210-219 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 126-132 22661948-7 2012 This model is able to simulate the pharmacokinetics (PK) after single and repeated oral tamoxifen doses in female breast cancer patients in dependence of the CYP2D6 phenotype. Tamoxifen 88-97 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 158-164 21823108-1 2012 BACKGROUND: Previous studies evaluating the effect of cytochrome P450 2D6 (CYP2D6) polymorphisms on outcomes of adjuvant tamoxifen therapy have been conflicting due to differences in study design, concomitant medications that alter CYP2D6 metabolism, and tamoxifen adherence. Tamoxifen 121-130 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 54-73 22395644-12 2012 CYP2D6 metabolism phenotype was associated with tamoxifen-induced hot flushes (P = .020). Tamoxifen 48-57 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 22395645-0 2012 CYP2D6 genotype as a marker for benefit of adjuvant tamoxifen in postmenopausal women: lessons learned. Tamoxifen 52-61 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 22180457-8 2012 In a combined analysis of rs10509373 genotype with previously identified genetic makers, CYP2D6 and ABCC2, the number of risk alleles of these three genes had cumulative effects on recurrence-free survival among 345 patients receiving tamoxifen monotherapy (log-rank P= 2.28 x 10(-12)). Tamoxifen 235-244 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 89-95 22515611-0 2012 Use of CYP2D6 genotyping in practice: tamoxifen dose adjustment. Tamoxifen 38-47 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 7-13 22515611-2 2012 Ultimate conversion of the parent drug by the enzyme CYP2D6 to the active metabolite, endoxifen, is required for tamoxifen to exert its anticancer effects. Tamoxifen 113-122 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 53-59 22395643-0 2012 CYP2D6 and UGT2B7 genotype and risk of recurrence in tamoxifen-treated breast cancer patients. Tamoxifen 53-62 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 22395643-2 2012 Previous studies have suggested that metabolic conversion of tamoxifen to endoxifen by cytochrome P450 2D6 (CYP2D6) is required for patient benefit from tamoxifen therapy. Tamoxifen 61-70 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 87-106 22395643-2 2012 Previous studies have suggested that metabolic conversion of tamoxifen to endoxifen by cytochrome P450 2D6 (CYP2D6) is required for patient benefit from tamoxifen therapy. Tamoxifen 61-70 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 108-114 22395643-2 2012 Previous studies have suggested that metabolic conversion of tamoxifen to endoxifen by cytochrome P450 2D6 (CYP2D6) is required for patient benefit from tamoxifen therapy. Tamoxifen 153-162 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 87-106 22395643-2 2012 Previous studies have suggested that metabolic conversion of tamoxifen to endoxifen by cytochrome P450 2D6 (CYP2D6) is required for patient benefit from tamoxifen therapy. Tamoxifen 153-162 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 108-114 22395644-2 2012 Cytochrome P450 2D6 (CYP2D6) enzyme metabolizes tamoxifen to clinically active metabolites, and CYP2D6 polymorphisms may adversely affect tamoxifen efficacy. Tamoxifen 48-57 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-19 22395644-2 2012 Cytochrome P450 2D6 (CYP2D6) enzyme metabolizes tamoxifen to clinically active metabolites, and CYP2D6 polymorphisms may adversely affect tamoxifen efficacy. Tamoxifen 48-57 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 21-27 22395644-2 2012 Cytochrome P450 2D6 (CYP2D6) enzyme metabolizes tamoxifen to clinically active metabolites, and CYP2D6 polymorphisms may adversely affect tamoxifen efficacy. Tamoxifen 138-147 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-19 22395644-2 2012 Cytochrome P450 2D6 (CYP2D6) enzyme metabolizes tamoxifen to clinically active metabolites, and CYP2D6 polymorphisms may adversely affect tamoxifen efficacy. Tamoxifen 138-147 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 21-27 22395644-2 2012 Cytochrome P450 2D6 (CYP2D6) enzyme metabolizes tamoxifen to clinically active metabolites, and CYP2D6 polymorphisms may adversely affect tamoxifen efficacy. Tamoxifen 138-147 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 96-102 22183189-0 2012 The risk of recurrence in breast cancer patients treated with tamoxifen: polymorphisms of CYP2D6 and ABCB1. Tamoxifen 62-71 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 90-96 22183189-1 2012 CYP2D6 plays a major role in the metabolism of tamoxifen, and polymorphism of P-glycoprotein has been associated with resistance of many drug therapies. Tamoxifen 47-56 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 22183189-2 2012 This study investigates the clinical impact of genetic variants of CYP2D6 and ABCB1 in breast cancer patients treated with tamoxifen. Tamoxifen 123-132 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 67-73 21823108-1 2012 BACKGROUND: Previous studies evaluating the effect of cytochrome P450 2D6 (CYP2D6) polymorphisms on outcomes of adjuvant tamoxifen therapy have been conflicting due to differences in study design, concomitant medications that alter CYP2D6 metabolism, and tamoxifen adherence. Tamoxifen 121-130 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 75-81 21823108-1 2012 BACKGROUND: Previous studies evaluating the effect of cytochrome P450 2D6 (CYP2D6) polymorphisms on outcomes of adjuvant tamoxifen therapy have been conflicting due to differences in study design, concomitant medications that alter CYP2D6 metabolism, and tamoxifen adherence. Tamoxifen 255-264 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 54-73 21823108-1 2012 BACKGROUND: Previous studies evaluating the effect of cytochrome P450 2D6 (CYP2D6) polymorphisms on outcomes of adjuvant tamoxifen therapy have been conflicting due to differences in study design, concomitant medications that alter CYP2D6 metabolism, and tamoxifen adherence. Tamoxifen 255-264 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 75-81 22108178-3 2012 Since clomiphene shares structural similarities with tamoxifen, which is predominantly bioactivated by the polymorphic cytochrome P450 (CYP) 2D6, we systematically explored clomiphene metabolism and action in vitro and in vivo by pharmacogenetic, -kinetic and -dynamic investigations. Tamoxifen 53-62 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 119-144 23464412-3 2012 Tamoxifen must be converted into its metabolite endoxifen for biologic effects; this conversion process is catalysed by highly polymorphic cytochrome P450 2D6 (CYP2D6). Tamoxifen 0-9 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 139-158 22553469-2 2012 Tamoxifen efficacy is mediated by its biotransformation, predominantly via the cytochrome P450 2D6 (CYP2D6) isoenzyme, to the active metabolite endoxifen. Tamoxifen 0-9 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 79-98 22553469-2 2012 Tamoxifen efficacy is mediated by its biotransformation, predominantly via the cytochrome P450 2D6 (CYP2D6) isoenzyme, to the active metabolite endoxifen. Tamoxifen 0-9 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 100-106 22499734-5 2012 The first example examines the value of comprehensive CYP2D6 genotyping in a study of tamoxifen resistance. Tamoxifen 86-95 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 54-60 22499734-6 2012 Tamoxifen is metabolized primarily by CYP2D6 to more active forms. Tamoxifen 0-9 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 38-44 23167378-0 2012 Impact of CYP2D6 polymorphisms on tamoxifen responses of women with breast cancer: a microarray-based study in Thailand. Tamoxifen 34-43 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 10-16 23167378-1 2012 This study was designed to investigate the frequency of CYP2D6 polymorphisms and evaluate the association between genetic polymorphisms of CYP2D6 and tamoxifen therapeutic outcome in Thai breast cancer patients. Tamoxifen 150-159 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 139-145 23167378-2 2012 We recruited 48 breast cancer patients who received adjuvant tamoxifen for evaluating CYP2D6 genetic polymorphisms using microarray-based technology. Tamoxifen 61-70 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 86-92 23464412-3 2012 Tamoxifen must be converted into its metabolite endoxifen for biologic effects; this conversion process is catalysed by highly polymorphic cytochrome P450 2D6 (CYP2D6). Tamoxifen 0-9 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 160-166 23464412-4 2012 This study surveyed copy number variation of the CYP2D6 gene and its possible correlation with Tamoxifen resistance in breast cancer patients. Tamoxifen 95-104 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 49-55 21437611-1 2012 Active metabolites of tamoxifen are formed mainly by the action of cytochrome P450 2D6 (CYP2D6). Tamoxifen 22-31 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 67-86 21947681-0 2012 Dose-adjustment study of tamoxifen based on CYP2D6 genotypes in Japanese breast cancer patients. Tamoxifen 25-34 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 44-50 21947681-1 2012 CYP2D6 is a key enzyme responsible for the metabolism of tamoxifen to active metabolites, endoxifen, and 4-hydroxytamoxifen. Tamoxifen 57-66 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 21437611-1 2012 Active metabolites of tamoxifen are formed mainly by the action of cytochrome P450 2D6 (CYP2D6). Tamoxifen 22-31 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 88-94 21947681-2 2012 The breast cancer patients who are heterozygous and homozygous for decreased-function and null alleles of CYP2D6 showed lower plasma concentrations of endoxifen and 4-hydroxytamoxifen compared to patients with homozygous-wild-type allele, resulting in worse clinical outcome in tamoxifen therapy. Tamoxifen 174-183 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 106-112 21947681-4 2012 For the patients who have one or no normal allele of CYP2D6, dosages of tamoxifen were increased to 30 and 40 mg/day, respectively. Tamoxifen 72-81 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 53-59 23226070-0 2012 CYP2D6 polymorphisms influence the efficacy of adjuvant tamoxifen in Thai breast cancer patients. Tamoxifen 56-65 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 21947681-9 2012 Plasma 4-hydroxytamoxifen concentrations in the patients with CYP2D6*1/*10 and CYP2D6*10/*10 were also significantly increased to the similar levels of the CYP2D6*1/*1 patients according to the increasing tamoxifen dosages (P < 0.001). Tamoxifen 16-25 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 62-68 21947681-9 2012 Plasma 4-hydroxytamoxifen concentrations in the patients with CYP2D6*1/*10 and CYP2D6*10/*10 were also significantly increased to the similar levels of the CYP2D6*1/*1 patients according to the increasing tamoxifen dosages (P < 0.001). Tamoxifen 16-25 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 79-85 21947681-9 2012 Plasma 4-hydroxytamoxifen concentrations in the patients with CYP2D6*1/*10 and CYP2D6*10/*10 were also significantly increased to the similar levels of the CYP2D6*1/*1 patients according to the increasing tamoxifen dosages (P < 0.001). Tamoxifen 16-25 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 79-85 22041137-3 2012 CYP2D6 is a key enzyme in this metabolic activation and it has been suggested that the genetic polymorphisms of CYP2D6 influence the plasma concentrations of active tamoxifen metabolites and clinical outcomes for breast cancer patients treated with tamoxifen. Tamoxifen 165-174 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 22041137-3 2012 CYP2D6 is a key enzyme in this metabolic activation and it has been suggested that the genetic polymorphisms of CYP2D6 influence the plasma concentrations of active tamoxifen metabolites and clinical outcomes for breast cancer patients treated with tamoxifen. Tamoxifen 165-174 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 112-118 22041137-3 2012 CYP2D6 is a key enzyme in this metabolic activation and it has been suggested that the genetic polymorphisms of CYP2D6 influence the plasma concentrations of active tamoxifen metabolites and clinical outcomes for breast cancer patients treated with tamoxifen. Tamoxifen 249-258 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 22041137-3 2012 CYP2D6 is a key enzyme in this metabolic activation and it has been suggested that the genetic polymorphisms of CYP2D6 influence the plasma concentrations of active tamoxifen metabolites and clinical outcomes for breast cancer patients treated with tamoxifen. Tamoxifen 249-258 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 112-118 22531359-2 2012 Bioconversion of tamoxifen to endoxifen, its most abundant active metabolite, is primarily dependent on the activity of cytochrome P450 2D6 (CYP2D6), which is highly polymorphic. Tamoxifen 17-26 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 120-139 22531359-2 2012 Bioconversion of tamoxifen to endoxifen, its most abundant active metabolite, is primarily dependent on the activity of cytochrome P450 2D6 (CYP2D6), which is highly polymorphic. Tamoxifen 17-26 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 141-147 22531359-3 2012 Over 20 published studies have reported on the potential association between CYP2D6 polymorphism and tamoxifen treatment outcome, with highly inconsistent results. Tamoxifen 101-110 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 77-83 22531359-7 2012 Future association studies on the link between CYP2D6 genotype and tamoxifen treatment efficacy should account for combination therapy and CYP2D6 inhibition, and interrogate as many CYP2D6 alleles as possible. Tamoxifen 67-76 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 47-53 23289191-0 2012 Side effects associated with ultrarapid cytochrome P450 2D6 genotype among women with early stage breast cancer treated with tamoxifen. Tamoxifen 125-134 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 40-59 23289191-1 2012 BACKGROUND: The side effects of tamoxifen, a drug widely used for the treatment and the prevention of recurrence in patients with estrogen receptor positive breast cancers (ER+), have been reported in clinical trials, but to date no information is available on their possible association with an increased enzymatic activity of CYP2D6 (ultra-metabolizers, UMs). Tamoxifen 32-41 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 328-334 23289191-7 2012 CONCLUSIONS: Our results suggest a new association between CYP2D6 gene duplication and side effects to tamoxifen, indicating a possible role of CYP2D6 in their occurrence. Tamoxifen 103-112 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 59-65 23289191-7 2012 CONCLUSIONS: Our results suggest a new association between CYP2D6 gene duplication and side effects to tamoxifen, indicating a possible role of CYP2D6 in their occurrence. Tamoxifen 103-112 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 144-150 23226070-1 2012 AIM: We evaluated single nucleotide polymorphisms (SNPs) of CYP2D6 to identify those that influence the efficiency of tamoxifen in adjuvant treatment of breast cancer through a matched case-control study. Tamoxifen 118-127 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 60-66 23226070-8 2012 CONCLUSIONS: This study demonstrated that CYP2D6*10/*10 was significantly associated with shorter DFS in Thai breast cancer patients receiving tamoxifen. Tamoxifen 143-152 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 42-48 21880792-1 2011 BACKGROUND: Controversy exists regarding the association between CYP2D6 enzyme activity and tamoxifen effectiveness in the adjuvant treatment of invasive breast cancer; however, this association in the primary prevention of breast cancer is unknown. Tamoxifen 92-101 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 65-71 22152167-3 2011 Pharmacogenetic testing efficacy is estimated by synthesizing randomized controlled trial data comparing tamoxifen to anastrozole with observational data linking CYP2D6 genotype to tamoxifen outcomes. Tamoxifen 181-190 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 162-168 22152167-8 2011 The most valuable research (VOI $53-$82 million) elucidates the relationship between CYP2D6 genotype and tamoxifen effectiveness. Tamoxifen 105-114 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 85-91 22152167-10 2011 CONCLUSIONS: Retrospective analysis of one of the large adjuvant aromatase inhibitor trials is warranted to better understand any association between CYP2D6 genotype and tamoxifen outcomes. Tamoxifen 170-179 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 150-156 22015273-9 2011 It is known that SSRIs block the CYP2D6 enzyme that metabolically activates tamoxifen to its potent anti-oestrogenic metabolite, endoxifen. Tamoxifen 76-85 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 33-39 21970596-3 2011 CYP2D6 testing among tamoxifen users offers a potential test case of the use of pharmacogenetic testing in the clinic. Tamoxifen 21-30 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 21961651-1 2011 AIM: Tamoxifen biotransformation to endoxifen, a potent antiestrogen, is catalyzed by CYP2D6. Tamoxifen 5-14 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 86-92 21906462-0 2011 The clinical effectiveness and cost-effectiveness of genotyping for CYP2D6 for the management of women with breast cancer treated with tamoxifen: a systematic review. Tamoxifen 135-144 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 68-74 21900890-0 2011 Increasing tamoxifen dose in breast cancer patients based on CYP2D6 genotypes and endoxifen levels: effect on active metabolite isomers and the antiestrogenic activity score. Tamoxifen 11-20 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 61-67 21900890-1 2011 Tamoxifen (Tam), the major drug for estrogen receptor (ER)-positive breast cancer, is converted to its active metabolites, Z- and Z"-endoxifen and 4-OH-Tam isomers, primarily by cytochrome P450 CYP2D6. Tamoxifen 0-9 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 194-200 21900890-1 2011 Tamoxifen (Tam), the major drug for estrogen receptor (ER)-positive breast cancer, is converted to its active metabolites, Z- and Z"-endoxifen and 4-OH-Tam isomers, primarily by cytochrome P450 CYP2D6. Tamoxifen 0-3 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 194-200 21900890-2 2011 In 117 patients taking 20 mg/day of Tam, we determined CYP2D6 genotypes and measured the plasma levels of Tam metabolites. Tamoxifen 36-39 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 55-61 25961262-7 2011 The assay was applied to type the CYP2D6 gene in 199 Austrian individuals including 106 breast cancer patients undergoing tamoxifen treatment. Tamoxifen 122-131 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 34-40 21750172-1 2011 BACKGROUND: Tamoxifen is oxidized by cytochrome-P450 enzymes (e.g., CYP2D6) to two active metabolites, which are eliminated via glucuronidation by UDP-glucuronosyl transferases (UGT). Tamoxifen 12-21 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 68-74 21906462-4 2011 TAM is known to be metabolised to its active metabolites N-desmethyl TAM and 4-hydroxytamoxifen by a number of CYP450 enzymes, including CYP2D6, CYP3A4, CYP2C9, CYP2C19 and CYP2B6. Tamoxifen 0-3 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 137-143 21906462-6 2011 Endoxifen, which is also formed via the action of CYP2D6, is 30- to 100-fold more potent than TAM in suppressing oestrogen-dependent cell proliferation, and is considered an entity responsible for significant pharmacological effects of TAM. Tamoxifen 236-239 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 50-56 21906462-13 2011 A review of economic evaluations and models of CYP2D6 testing for patients treated with TAM was also carried out. Tamoxifen 88-91 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 47-53 21860550-0 2011 Association between genetic polymorphisms of CYP2D6 and outcomes in breast cancer patients with tamoxifen treatment. Tamoxifen 96-105 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 45-51 21768449-1 2011 PURPOSE: Tamoxifen, a widely used agent for the prevention and treatment of breast cancer, is mainly metabolized by CYP2D6 and CYP3A to form its most abundant active metabolite, endoxifen. Tamoxifen 9-18 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 116-122 21768473-0 2011 Genotype-guided tamoxifen dosing increases active metabolite exposure in women with reduced CYP2D6 metabolism: a multicenter study. Tamoxifen 16-25 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 92-98 21860550-1 2011 The aim of the study was to evaluate the association between genetic polymorphisms of CYP2D6 and outcomes in breast cancer patients with tamoxifen treatment. Tamoxifen 137-146 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 86-92 21527579-1 2011 BACKGROUND: The gene encoding the phase I enzyme cytochrome P4502D6 (CYP2D6) has been previously investigated for its potential predictive role in the efficacy of breast cancer treatments such as tamoxifen, but its role in breast cancer susceptibility is unclear. Tamoxifen 196-205 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 49-67 21751753-3 2011 Co-administration of tamoxifen with isoenzyme CYP 2D6 inhibitors reduces this metabolism. Tamoxifen 21-30 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 46-53 21751753-9 2011 It is better to avoid prescribing isoenzyme CYP 2D6 inhibitors to women treated with tamoxifen for breast cancer, especially SSRI antidepressants such as paroxetine and fluoxetine. Tamoxifen 85-94 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 44-51 21830868-1 2011 AIMS: Tamoxifen is metabolized by cytochrome P450s, with an important role for CYP2D6. Tamoxifen 6-15 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 79-85 21527579-1 2011 BACKGROUND: The gene encoding the phase I enzyme cytochrome P4502D6 (CYP2D6) has been previously investigated for its potential predictive role in the efficacy of breast cancer treatments such as tamoxifen, but its role in breast cancer susceptibility is unclear. Tamoxifen 196-205 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 69-75 21185724-5 2011 Retrospective clinical data suggests that specific single nucleotide polymorphisms (SNPs) of CYP2D6 can lead to null or reduced enzyme activity resulting in worse outcomes for those individuals when treated with tamoxifen for HR positive breast cancer. Tamoxifen 212-221 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 93-99 21480951-1 2011 AIM: To investigate the impact of genetic polymorphisms in CYP2D6, CYP3A5, CYP2C9 and CYP2C19 on the pharmacokinetics of tamoxifen and its metabolites in Asian breast cancer patients. Tamoxifen 121-130 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 59-65 21480951-8 2011 Similar relationships were observed between the CYP2D6 polymorphisms and metabolic ratios of tamoxifen and its metabolites. Tamoxifen 93-102 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 48-54 21480951-10 2011 CONCLUSIONS: The present study in Asian breast cancer patients showed that CYP2D6*5/*10 and *10/*10 genotypes are associated with significantly lower concentrations of the active metabolite of tamoxifen, endoxifen. Tamoxifen 193-202 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 75-81 21709817-2 2011 Tamoxifen is metabolized by several polymorphic enzymes, including cytochrome P450 2D6 (CYP2D6), to more active metabolites. Tamoxifen 0-9 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 67-86 21709817-2 2011 Tamoxifen is metabolized by several polymorphic enzymes, including cytochrome P450 2D6 (CYP2D6), to more active metabolites. Tamoxifen 0-9 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 88-94 21709817-3 2011 We have reviewed the clinical pharmacology of tamoxifen and evaluated the evidence from clinical epidemiology studies regarding the association between CYP2D6 inhibition and tamoxifen effectiveness. Tamoxifen 174-183 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 152-158 21709817-4 2011 We conclude that the impact of CYP2D6 inhibition on tamoxifen effectiveness is likely to be null or small, at least in the populations studied so far. Tamoxifen 52-61 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 31-37 20848186-1 2011 Concurrent use of tamoxifen and cytochrome P450 2D6 (CYP2D6) inhibitors, such as selective serotonin reuptake inhibitors, has been shown to decrease plasma concentrations of tamoxifen metabolites. Tamoxifen 18-27 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 53-59 20848186-1 2011 Concurrent use of tamoxifen and cytochrome P450 2D6 (CYP2D6) inhibitors, such as selective serotonin reuptake inhibitors, has been shown to decrease plasma concentrations of tamoxifen metabolites. Tamoxifen 174-183 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 32-51 20848186-1 2011 Concurrent use of tamoxifen and cytochrome P450 2D6 (CYP2D6) inhibitors, such as selective serotonin reuptake inhibitors, has been shown to decrease plasma concentrations of tamoxifen metabolites. Tamoxifen 174-183 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 53-59 21451508-1 2011 The therapeutic effect of tamoxifen depends on active metabolites, e.g., cytochrome P450 2D6 (CYP2D6) mediated formation of endoxifen. Tamoxifen 26-35 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 73-92 21451508-1 2011 The therapeutic effect of tamoxifen depends on active metabolites, e.g., cytochrome P450 2D6 (CYP2D6) mediated formation of endoxifen. Tamoxifen 26-35 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 94-100 21451508-5 2011 Among the poor metabolizers, 93% had (Z)-endoxifen levels below IC90 values, underscoring the role of CYP2D6 deficiency in compromised tamoxifen bioactivation. Tamoxifen 135-144 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 102-108 21185724-3 2011 Tamoxifen is a pro-drug that is metabolised to its active metabolites by the cytochrome P450 (CYP) enzymes including CYP2D6, CYP3A, CYP2B6, and CYP2C19. Tamoxifen 0-9 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 117-123 21185724-7 2011 Commercial tests are now available for the genotyping of CYP2D6 with the aim of individualisation of tamoxifen therapy for patients with HR positive breast cancer. Tamoxifen 101-110 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 57-63 21185724-9 2011 These drugs potently inhibit the metabolism of tamoxifen by CYP2D6 and thus potentially may lessen the efficacy of tamoxifen. Tamoxifen 47-56 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 60-66 21185724-9 2011 These drugs potently inhibit the metabolism of tamoxifen by CYP2D6 and thus potentially may lessen the efficacy of tamoxifen. Tamoxifen 115-124 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 60-66 21185724-11 2011 This review article will summarize the available published breast cancer data on the interaction between the relevant SNPs for CYP2D6, CYP3A, CYP2B6, and CYP2C19 and the efficacy of tamoxifen, their role in individualisation of hormonal therapy and the role of the commercially available genotyping kits. Tamoxifen 182-191 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 127-133 20309015-0 2011 Efficacy of tamoxifen based on cytochrome P450 2D6, CYP2C19 and SULT1A1 genotype in the Italian Tamoxifen Prevention Trial. Tamoxifen 12-21 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 31-50 20309015-9 2011 Tamoxifen showed reduced efficacy in CYP2D6 PMs in the chemoprevention setting. Tamoxifen 0-9 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 37-43 20309015-10 2011 Conversely, the CYP2D6*2A allele may be associated with increased efficacy of tamoxifen. Tamoxifen 78-87 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 16-22 21226615-5 2011 Multiple studies suggest that women who carry one or two variant CYP2D6 alleles that encode enzymes with null or reduced activity may have an inferior breast cancer outcome when treated with tamoxifen in the adjuvant setting compared to women carrying two alleles encoding an enzyme with normal activity. Tamoxifen 191-200 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 65-71 21325141-1 2011 BACKGROUND: Cytochrome P450 2D6 (CYP2D6) inhibition reduces the concentration of 4-hydroxylated tamoxifen metabolites, but the clinical relevance remains uncertain. Tamoxifen 96-105 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 12-31 21325141-1 2011 BACKGROUND: Cytochrome P450 2D6 (CYP2D6) inhibition reduces the concentration of 4-hydroxylated tamoxifen metabolites, but the clinical relevance remains uncertain. Tamoxifen 96-105 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 33-39 21325141-11 2011 CONCLUSION: The association between CYP2D6 inhibition and recurrence in tamoxifen-treated patients is likely null or small. Tamoxifen 72-81 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 36-42 21392396-10 2011 Additionally, low concentrations of endoxifen observed in tamoxifen treated patients with deficient CYP2D6 activity (20 to 40 nM) markedly inhibit estrogen-induced cell proliferation rates in the presence of ERbeta, whereas much higher endoxifen concentrations are needed when ERbeta is absent. Tamoxifen 58-67 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 100-106 21148080-1 2011 Tamoxifen is widely prescribed to patients with estrogen receptor-positive breast cancer, and it is a prodrug that requires bioactivation by cytochrome P450 enzymes CYP2D6 and 3A4 to generate the active metabolite, endoxifen. Tamoxifen 0-9 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 165-171 21342038-2 2011 Because CYP2D6 is known to be a key enzyme responsible for the generation of an active tamoxifen metabolite, "endoxifen", some studies reported that genetic polymorphisms of CYP2D6 that reduced its enzyme activity or coadministration of CYP2D6 inhibitors were associated with the poor clinical outcomes of breast cancer patients treated with tamoxifen. Tamoxifen 87-96 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 174-180 21342038-2 2011 Because CYP2D6 is known to be a key enzyme responsible for the generation of an active tamoxifen metabolite, "endoxifen", some studies reported that genetic polymorphisms of CYP2D6 that reduced its enzyme activity or coadministration of CYP2D6 inhibitors were associated with the poor clinical outcomes of breast cancer patients treated with tamoxifen. Tamoxifen 342-351 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 8-14 21342038-2 2011 Because CYP2D6 is known to be a key enzyme responsible for the generation of an active tamoxifen metabolite, "endoxifen", some studies reported that genetic polymorphisms of CYP2D6 that reduced its enzyme activity or coadministration of CYP2D6 inhibitors were associated with the poor clinical outcomes of breast cancer patients treated with tamoxifen. Tamoxifen 342-351 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 174-180 21342038-2 2011 Because CYP2D6 is known to be a key enzyme responsible for the generation of an active tamoxifen metabolite, "endoxifen", some studies reported that genetic polymorphisms of CYP2D6 that reduced its enzyme activity or coadministration of CYP2D6 inhibitors were associated with the poor clinical outcomes of breast cancer patients treated with tamoxifen. Tamoxifen 342-351 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 174-180 21342038-3 2011 However, there are some discrepant reports for the association between CYP2D6 genotype and clinical outcomes of tamoxifen therapy, probably because of the heterogeneity in sample collection or analysis, including differences in regimen of tamoxifen treatment. Tamoxifen 112-121 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 71-77 21342038-3 2011 However, there are some discrepant reports for the association between CYP2D6 genotype and clinical outcomes of tamoxifen therapy, probably because of the heterogeneity in sample collection or analysis, including differences in regimen of tamoxifen treatment. Tamoxifen 239-248 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 71-77 21342038-4 2011 A review of published reports regarding the effects of selective serotonin reuptake inhibitors on the pharmacokinetics and/or efficacy of tamoxifen found that concurrent use of strong CYP2D6 inhibitors, especially paroxetine, and possibly others, should be avoided in patients receiving tamoxifen therapy, but there has not been enough evidence for the effects of weak or moderate inhibitors. Tamoxifen 138-147 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 184-190 21421116-4 2011 Relative resistance to tamoxifen treatment may be a result, in part, from impaired drug activation by cytochrome P450 2D6 (CYP2D6). Tamoxifen 23-32 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 102-121 21421116-4 2011 Relative resistance to tamoxifen treatment may be a result, in part, from impaired drug activation by cytochrome P450 2D6 (CYP2D6). Tamoxifen 23-32 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 123-129 21421116-5 2011 Indeed, recent studies have identified allelic variations in CYP2D6 to be an important determinant of tamoxifen"s activity (and toxicity). Tamoxifen 102-111 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 61-67 21421116-6 2011 This article will summarize the current information regarding the influence of the major genotypes and CYP2D6 inhibitors on tamoxifen metabolism, with a focus on its clinical utility and the current level of evidence for CYP2D6 genotyping of patients who are candidates for tamoxifen treatment. Tamoxifen 124-133 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 103-109 21342038-2 2011 Because CYP2D6 is known to be a key enzyme responsible for the generation of an active tamoxifen metabolite, "endoxifen", some studies reported that genetic polymorphisms of CYP2D6 that reduced its enzyme activity or coadministration of CYP2D6 inhibitors were associated with the poor clinical outcomes of breast cancer patients treated with tamoxifen. Tamoxifen 87-96 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 8-14 21342038-2 2011 Because CYP2D6 is known to be a key enzyme responsible for the generation of an active tamoxifen metabolite, "endoxifen", some studies reported that genetic polymorphisms of CYP2D6 that reduced its enzyme activity or coadministration of CYP2D6 inhibitors were associated with the poor clinical outcomes of breast cancer patients treated with tamoxifen. Tamoxifen 87-96 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 174-180 21226615-7 2011 CYP2D6 activity can also be reduced by concomitant use of drugs that inhibit the enzyme, including antidepressants used for psychiatric conditions or to relieve hot flashes, and these should be avoided in tamoxifen users whenever possible. Tamoxifen 205-214 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 21875255-7 2011 CYP2D6 variants have been correlated with tamoxifen response and interindividual variability seen. Tamoxifen 42-51 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 20593233-1 2011 Endoxifen, the most active metabolite of the prodrug tamoxifen, is produced by cytochrome P450 CYP2D6. Tamoxifen 53-62 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 95-101 20593233-2 2011 Breast cancer patients treated with tamoxifen who have reduced CYP2D6 activity, related to either genetic variation or drug inhibition, may have inferior outcomes. Tamoxifen 36-45 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 63-69 20809362-1 2011 The association between CYP2D6 genotype and outcome in breast cancer patients treated with adjuvant tamoxifen remains controversial. Tamoxifen 100-109 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 24-30 20593233-6 2011 Patients were classified as users of CYP2D6 inhibitors if they purchased strong CYP2D6 inhibiting drugs for >= 4 consecutive months during tamoxifen treatment. Tamoxifen 142-151 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 37-43 20809362-0 2011 Comprehensive CYP2D6 genotype and adherence affect outcome in breast cancer patients treated with tamoxifen monotherapy. Tamoxifen 98-107 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 14-20 20809362-8 2011 The effect of CYP2D6 genotype was increased by adjusting for adherence to tamoxifen therapy, but not significantly changed when adjusted for co-administration of potent inhibitors of CYP2D6. Tamoxifen 74-83 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 14-20 20809362-9 2011 Comprehensive genotyping of CYP2D6 and adherence to tamoxifen therapy may be useful to identify breast cancer patients most likely to benefit from adjuvant tamoxifen. Tamoxifen 156-165 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 28-34 21526323-3 2011 Some antidepressants could potentially inhibit cytochrome P450 2D6, required to activate tamoxifen, interfering with its action. Tamoxifen 89-98 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 47-66 21526323-4 2011 Although there is not a clear cut directive on the subject, it is nowadays recommended to treat women with antidepressants with the lower cytochrome P450 2D6 inhibition potential to avoid a possible antagonism that may reduce tamoxifen s prevention of breast cancer recurrence at least in some patients with CYP2D6 genetic variation. Tamoxifen 226-235 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 138-157 20880642-10 2010 Paroxetine, fluoxetine and bupropion are strong CYP2D6 inhibitors which should be avoided in tamoxifen users. Tamoxifen 93-102 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 48-54 21086978-1 2010 Tamoxifen (Tam), the antiestrogen used to treat estrogen receptor-positive breast cancer is a pro-drug that is converted to its major active metabolites, endoxifen and 4-hydroxy-tamoxifen (4-OH-Tam) by various biotransformation enzymes of which cytochrome P450-2D6 (CYP2D6) is key. Tamoxifen 0-9 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 245-264 21086978-1 2010 Tamoxifen (Tam), the antiestrogen used to treat estrogen receptor-positive breast cancer is a pro-drug that is converted to its major active metabolites, endoxifen and 4-hydroxy-tamoxifen (4-OH-Tam) by various biotransformation enzymes of which cytochrome P450-2D6 (CYP2D6) is key. Tamoxifen 0-9 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 266-272 21086978-1 2010 Tamoxifen (Tam), the antiestrogen used to treat estrogen receptor-positive breast cancer is a pro-drug that is converted to its major active metabolites, endoxifen and 4-hydroxy-tamoxifen (4-OH-Tam) by various biotransformation enzymes of which cytochrome P450-2D6 (CYP2D6) is key. Tamoxifen 0-3 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 245-264 21086978-1 2010 Tamoxifen (Tam), the antiestrogen used to treat estrogen receptor-positive breast cancer is a pro-drug that is converted to its major active metabolites, endoxifen and 4-hydroxy-tamoxifen (4-OH-Tam) by various biotransformation enzymes of which cytochrome P450-2D6 (CYP2D6) is key. Tamoxifen 0-3 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 266-272 20981001-2 2010 In order to be clinically effective, tamoxifen must be converted to endoxifen by cytochrome P450 2D6 (CYP2D6). Tamoxifen 37-46 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 81-100 20981001-2 2010 In order to be clinically effective, tamoxifen must be converted to endoxifen by cytochrome P450 2D6 (CYP2D6). Tamoxifen 37-46 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 102-108 20827267-7 2010 However, the following observations from the original report did not change: (i) the levels of circulating lipids are lower in women taking tamoxifen; (ii) there is an association between the ESR2-02 genotypes and changes in triglyceride levels; and (iii) neither ESR1 PvuII nor CYP2D6 is associated with any changes in serum lipid concentrations in patients receiving treatment with tamoxifen. Tamoxifen 140-149 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 279-285 21152250-5 2010 We used TaqMan assays to determine the genotypes of three enzyme variants hypothesized to modify tamoxifen effectiveness, ie, CYP2D6*4, UGT2B15*2, and UGT1A8*2. Tamoxifen 97-106 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 126-132 20849243-0 2010 Impact of CYP2D6*4 genotype on progression free survival in tamoxifen breast cancer treatment. Tamoxifen 60-69 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 10-16 20849243-1 2010 OBJECTIVE: The cytochrome P450 2D6 (CYP2D6) polymorphism was reported to have a significant impact on outcome of tamoxifen treatment in estrogen receptor positive breast cancer patients. Tamoxifen 113-122 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 15-34 20849243-1 2010 OBJECTIVE: The cytochrome P450 2D6 (CYP2D6) polymorphism was reported to have a significant impact on outcome of tamoxifen treatment in estrogen receptor positive breast cancer patients. Tamoxifen 113-122 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 36-42 20849243-2 2010 The objective of this study was to explore the effect of the CYP2D6*4 polymorphism on tamoxifen treatment outcome in a cohort of patients from a single clinical trial which included women with a history of previous chemotherapy. Tamoxifen 86-95 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 61-67 20628863-3 2010 To address this issue, we examined the methylation pattern and expression of the selected genes coding for drug-metabolizing enzymes, including COMT, CYP1A1, CYP2D6, NAT1, and SULT1A1 in tamoxifen-resistant and control breast cancers. Tamoxifen 187-196 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 158-164 20823421-0 2010 Avoidance of CYP2D6 inhibitors in patients receiving tamoxifen. Tamoxifen 53-62 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 13-19 20700120-0 2010 The impact of CYP2D6-predicted phenotype on tamoxifen treatment outcome in patients with metastatic breast cancer. Tamoxifen 44-53 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 14-20 20700120-1 2010 BACKGROUND: Cytochrome P450 2D6 (CYP2D6) has a crucial role in the metabolic conversion of tamoxifen into the active metabolite endoxifen. Tamoxifen 91-100 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 12-31 20700120-1 2010 BACKGROUND: Cytochrome P450 2D6 (CYP2D6) has a crucial role in the metabolic conversion of tamoxifen into the active metabolite endoxifen. Tamoxifen 91-100 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 33-39 20700120-2 2010 In this cohort study, the effect of CYP2D6-predicted phenotype, defined as the combined effect of CYP2D6 genetic variation and concomitant use of CYP2D6-inhibiting medication, on time to breast cancer progression (TTP) and overall survival (OS) in women who use tamoxifen for metastatic breast cancer (MBC) was examined. Tamoxifen 262-271 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 36-42 20700120-7 2010 CONCLUSION: CYP2D6 phenotype is an important predictor of treatment outcome in women who are receiving tamoxifen for MBC. Tamoxifen 103-112 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 12-18 20700120-8 2010 Co-administration of CYP2D6 inhibitors worsens treatment outcome of tamoxifen and should therefore be handled with care. Tamoxifen 68-77 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 21-27 20877451-0 2010 CYP2D6 testing to predict response to tamoxifen in women with breast cancer. Tamoxifen 38-47 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 20877451-5 2010 Cytochrome P450 (CYP) enzymes, CYP2D6 in particular, play a major role in the metabolism of tamoxifen to active metabolites. Tamoxifen 92-101 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 31-37 20515869-0 2010 CYP2D6 polymorphisms as predictors of outcome in breast cancer patients treated with tamoxifen: expanded polymorphism coverage improves risk stratification. Tamoxifen 85-94 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 20515869-1 2010 PURPOSE: This study aimed to validate matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS)/Taqman copy number assay (CNA) CYP2D6 genotyping by AmpliChip CYP450 Test for the prediction of tamoxifen metabolizer phenotypes in breast cancer, and to investigate the influence of CYP2D6 variant coverage on genotype-phenotype relationships and tamoxifen outcome. Tamoxifen 226-235 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 161-167 20515869-1 2010 PURPOSE: This study aimed to validate matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS)/Taqman copy number assay (CNA) CYP2D6 genotyping by AmpliChip CYP450 Test for the prediction of tamoxifen metabolizer phenotypes in breast cancer, and to investigate the influence of CYP2D6 variant coverage on genotype-phenotype relationships and tamoxifen outcome. Tamoxifen 377-386 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 161-167 20515869-11 2010 For tamoxifen pharmacogenetics, broad CYP2D6 allele coverage is recommended to reduce phenotype misclassification. Tamoxifen 4-13 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 38-44 20574415-0 2010 Lessons for pharmacogenomics studies: association study between CYP2D6 genotype and tamoxifen response. Tamoxifen 84-93 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 64-70 19995676-7 2010 Third, the influence of CYP2D6 on tamoxifen efficacy, a model candidate with potential clinical utility but unclear validity. Tamoxifen 34-43 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 24-30 20651057-1 2010 Genetic variants in CYP2D6 lead to reduced conversion of tamoxifen to the active metabolite endoxifen. Tamoxifen 57-66 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 20-26 20651057-2 2010 However, the role of the CYP2D6 genotype in predicting tamoxifen-associated outcomes remains controversial. Tamoxifen 55-64 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 25-31 20651057-3 2010 Accurate assignment of the CYP2D6 genotype in archival tissues is crucial for future studies attempting to determine risk prediction of outcomes in tamoxifen-treated individuals. Tamoxifen 148-157 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 27-33 20574415-1 2010 We earlier reported a significant association between the cytochrome P450 2D6 (CYP2D6) genotype and the clinical outcome in 282 Japanese breast cancer patients receiving tamoxifen monotherapy. Tamoxifen 170-179 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 58-77 20574415-1 2010 We earlier reported a significant association between the cytochrome P450 2D6 (CYP2D6) genotype and the clinical outcome in 282 Japanese breast cancer patients receiving tamoxifen monotherapy. Tamoxifen 170-179 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 79-85 20574415-2 2010 Although many research groups have provided evidence indicating the CYP2D6 genotype as one of the strongest predictors of tamoxifen response, the results still remain controversial. Tamoxifen 122-131 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 68-74 20574415-5 2010 When we carried out two subgroup analyses for nodal status and tumor size, we observed a positive association between the CYP2D6 genotype and the clinical outcome only in patients who received tamoxifen monotherapy. Tamoxifen 193-202 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 122-128 20081063-0 2010 Composite functional genetic and comedication CYP2D6 activity score in predicting tamoxifen drug exposure among breast cancer patients. Tamoxifen 82-91 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 46-52 20966889-0 2010 Update on CYP2D6 and its impact on tamoxifen therapy. Tamoxifen 35-44 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 10-16 20052538-2 2010 Orally administered tamoxifen, is extensively metabolized by cytochrome P450 (CYP) enzymes, namely CYP3A4 and CYP2D6, into active metabolites, especially endoxifen. Tamoxifen 20-29 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 110-116 20052538-3 2010 Due to genetic polymorphism of CYP2D6, significant numbers of women metabolize tamoxifen to varying degree and may not receive the optimal benefit from tamoxifen treatment. Tamoxifen 79-88 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 31-37 20052538-3 2010 Due to genetic polymorphism of CYP2D6, significant numbers of women metabolize tamoxifen to varying degree and may not receive the optimal benefit from tamoxifen treatment. Tamoxifen 152-161 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 31-37 20439629-1 2010 Evidence has emerged that the clinical benefit of tamoxifen is related to the functional status of the hepatic metabolizing enzyme cytochrome P450 2D6 (CYP2D6). Tamoxifen 50-59 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 131-150 20439629-1 2010 Evidence has emerged that the clinical benefit of tamoxifen is related to the functional status of the hepatic metabolizing enzyme cytochrome P450 2D6 (CYP2D6). Tamoxifen 50-59 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 152-158 20439629-2 2010 CYP2D6 is the key enzyme responsible for the generation of the potent tamoxifen metabolite, endoxifen. Tamoxifen 70-79 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 20439629-3 2010 Multiple studies have examined the relationship of CYP2D6 status to breast cancer outcomes in tamoxifen-treated women; the majority of studies demonstrated that women with impaired CYP2D6 metabolism have lower endoxifen concentrations and a greater risk of breast cancer recurrence. Tamoxifen 94-103 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 51-57 20439629-3 2010 Multiple studies have examined the relationship of CYP2D6 status to breast cancer outcomes in tamoxifen-treated women; the majority of studies demonstrated that women with impaired CYP2D6 metabolism have lower endoxifen concentrations and a greater risk of breast cancer recurrence. Tamoxifen 94-103 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 181-187 20439629-4 2010 As a result, practitioners must be aware that some of the most commonly prescribed medications coadministered with tamoxifen interfere with CYP2D6 function, thereby reducing endoxifen concentrations and potentially increasing the risk of breast cancer recurrence. Tamoxifen 115-124 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 140-146 20439629-5 2010 After reviewing the published data regarding tamoxifen metabolism and the evidence relating CYP2D6 status to breast cancer outcomes in tamoxifen-treated patients, we are providing a guide for the use of medications that inhibit CYP2D6 in patients administered tamoxifen. Tamoxifen 45-54 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 228-234 20439629-5 2010 After reviewing the published data regarding tamoxifen metabolism and the evidence relating CYP2D6 status to breast cancer outcomes in tamoxifen-treated patients, we are providing a guide for the use of medications that inhibit CYP2D6 in patients administered tamoxifen. Tamoxifen 135-144 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 92-98 20439629-5 2010 After reviewing the published data regarding tamoxifen metabolism and the evidence relating CYP2D6 status to breast cancer outcomes in tamoxifen-treated patients, we are providing a guide for the use of medications that inhibit CYP2D6 in patients administered tamoxifen. Tamoxifen 135-144 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 228-234 20439629-5 2010 After reviewing the published data regarding tamoxifen metabolism and the evidence relating CYP2D6 status to breast cancer outcomes in tamoxifen-treated patients, we are providing a guide for the use of medications that inhibit CYP2D6 in patients administered tamoxifen. Tamoxifen 135-144 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 92-98 20439629-5 2010 After reviewing the published data regarding tamoxifen metabolism and the evidence relating CYP2D6 status to breast cancer outcomes in tamoxifen-treated patients, we are providing a guide for the use of medications that inhibit CYP2D6 in patients administered tamoxifen. Tamoxifen 135-144 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 228-234 20385997-1 2010 PURPOSE: The use of cytochrome P450 2D6-inhibiting drugs (CYP2D6 inhibitors) during tamoxifen treatment leads to a decrease in plasma concentration of endoxifen, the major active tamoxifen metabolite. Tamoxifen 84-93 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 58-64 20385997-1 2010 PURPOSE: The use of cytochrome P450 2D6-inhibiting drugs (CYP2D6 inhibitors) during tamoxifen treatment leads to a decrease in plasma concentration of endoxifen, the major active tamoxifen metabolite. Tamoxifen 179-188 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 58-64 20385997-2 2010 Concomitant use of CYP2D6 inhibitors, such as selective serotonin reuptake inhibitors, as well as low tamoxifen adherence may negatively impact tamoxifen efficacy in patients with breast cancer. Tamoxifen 144-153 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 19-25 20385997-8 2010 RESULTS: In total, 1,962 patients with breast cancer using tamoxifen were included, among whom 150 (7.6%) frequently used a CYP2D6 inhibitor during tamoxifen treatment. Tamoxifen 148-157 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 124-130 27713292-0 2010 The Impact of CYP2D6 Genotyping on Tamoxifen Treatment. Tamoxifen 35-44 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 14-20 27713292-2 2010 Tamoxifen efficacy depends on the biotransformation, predominantly via the cytochrome P450 2D6 (CYP2D6) isoform, to the active metabolite endoxifen. Tamoxifen 0-9 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 75-94 27713292-2 2010 Tamoxifen efficacy depends on the biotransformation, predominantly via the cytochrome P450 2D6 (CYP2D6) isoform, to the active metabolite endoxifen. Tamoxifen 0-9 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 96-102 27713292-3 2010 Both genetic and environmental (drug-induced) factors may alter CYP2D6 enzyme activity directly affecting the concentrations of active tamoxifen metabolites. Tamoxifen 135-144 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 64-70 27713292-4 2010 Several studies suggest that germline genetic variants in CYP2D6 influence the clinical outcomes of patients treated with adjuvant tamoxifen. Tamoxifen 131-140 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 58-64 27713292-5 2010 Here, we review the existing data relating CYP2D6 genotypes to tamoxifen efficacy. Tamoxifen 63-72 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 43-49 20454926-1 2010 Pharmacological evidence shows that cytochrome P450 2D6 (CYP2D6) function is important in the conversion of tamoxifen to its active metabolites. Tamoxifen 108-117 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 36-55 20454926-1 2010 Pharmacological evidence shows that cytochrome P450 2D6 (CYP2D6) function is important in the conversion of tamoxifen to its active metabolites. Tamoxifen 108-117 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 57-63 20454926-2 2010 Many retrospective analyses have assessed the role of both CYP2D6 genotype and concurrent administration of drug inhibitors of CYP2D6 on outcome of tamoxifen therapy. Tamoxifen 148-157 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 59-65 20454926-2 2010 Many retrospective analyses have assessed the role of both CYP2D6 genotype and concurrent administration of drug inhibitors of CYP2D6 on outcome of tamoxifen therapy. Tamoxifen 148-157 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 127-133 20454926-10 2010 Pooling of data from two studies evaluating CYP2D6 drug inhibitors showed that concomitant administration of these with tamoxifen was associated with a non-significant association with DFS (HR 1.37, 95% CI 0.69-2.73, P = 0.37). Tamoxifen 120-129 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 44-50 20507880-8 2010 Third, the interaction between phase I and II drug-metabolizing enzymes was demonstrated by MN induction with inhibitors of uridine diphosphate (UDP)-glucuronosyltransferases in tamoxifen-treated transformants harboring the corresponding CYP3A4 or with inhibitors of glutathione S-transferase in safrole-treated transformants harboring the corresponding CYP2D6, whereas neither tamoxifen nor safrole alone induced MN in any transformant. Tamoxifen 178-187 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 354-360 20467479-6 2010 In one example, thirty five CYP2D6 genotypes were partitioned into three groups to predict pharmacokinetics of a breast cancer drug, Tamoxifen, a CYP2D6 substrate (p-value = 0.04). Tamoxifen 133-142 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 28-34 20156115-3 2010 Cytochrome P-450 2D6 (CYP2D6) metabolizes SSRIs and also metabolizes tamoxifen to more active forms. Tamoxifen 69-78 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-20 20156115-3 2010 Cytochrome P-450 2D6 (CYP2D6) metabolizes SSRIs and also metabolizes tamoxifen to more active forms. Tamoxifen 69-78 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 22-28 20089828-0 2010 Pharmacogenetic-based clinical scores: a useful, simple tool to predict tamoxifen-based CYP2D6 phenotype? Tamoxifen 72-81 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 88-94 20124162-0 2010 Evidence and practice regarding the role for CYP2D6 inhibition in decisions about tamoxifen therapy. Tamoxifen 82-91 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 45-51 20124171-0 2010 Significant effect of polymorphisms in CYP2D6 and ABCC2 on clinical outcomes of adjuvant tamoxifen therapy for breast cancer patients. Tamoxifen 89-98 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 39-45 20124171-2 2010 We investigated relationships of polymorphisms in transporter genes and CYP2D6 to clinical outcome of patients receiving tamoxifen. Tamoxifen 121-130 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 72-78 20124171-11 2010 CONCLUSION: Our results suggest that polymorphisms in CYP2D6 and ABCC2 are important predictors for the prognosis of patients with breast cancer treated with tamoxifen. Tamoxifen 158-167 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 54-60 20731819-0 2010 CYP2D6 gene variants: association with breast cancer specific survival in a cohort of breast cancer patients from the United Kingdom treated with adjuvant tamoxifen. Tamoxifen 155-164 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 20123649-4 2010 Six retrospectives studies suggest a link between some polymorphisms of the CYP2D6 and tamoxifen efficacy and two studies have found no statistically significant data. Tamoxifen 87-96 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 76-82 20142325-1 2010 OBJECTIVE: To characterise whether some selective serotonin reuptake inhibitor (SSRI) antidepressants reduce tamoxifen"s effectiveness by inhibiting its bioactivation by cytochrome P450 2D6 (CYP2D6). Tamoxifen 109-118 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 170-189 20142325-1 2010 OBJECTIVE: To characterise whether some selective serotonin reuptake inhibitor (SSRI) antidepressants reduce tamoxifen"s effectiveness by inhibiting its bioactivation by cytochrome P450 2D6 (CYP2D6). Tamoxifen 109-118 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 191-197 20731819-3 2010 CYP2D6 variants resulting in poor metabolism of tamoxifen are hypothesised to reduce its efficacy. Tamoxifen 48-57 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 20731819-5 2010 However, evidence from published studies evaluating CYP2D6 variants as predictive factors of tamoxifen efficacy and clinical outcome are conflicting, querying the clinical utility of CYP2D6 testing. Tamoxifen 93-102 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 52-58 20731819-6 2010 We investigated the association of CYP2D6 variants with breast cancer specific survival (BCSS) in breast cancer patients receiving tamoxifen. Tamoxifen 131-140 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 35-41 20731819-11 2010 RESULTS: In tamoxifen treated patients, there was weak evidence that the poor-metaboliser variant, CYP2D6*6 (MAF = 0.01), was associated with decreased BCSS (P = 0.02; HR = 1.95; 95% CI = 1.12-3.40). Tamoxifen 12-21 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 99-105 20731819-13 2010 CONCLUSIONS: CYP2D6*6 may affect BCSS in tamoxifen-treated patients. Tamoxifen 41-50 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 13-19 21152245-10 2010 In conclusion, beyond reinforcing a role for CYP2D6 in tamoxifen response, our pathway analysis strongly suggests that specific combinations of allelic variants in other genes make major contributions to the tamoxifen-resistance phenotype. Tamoxifen 55-64 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 45-51 20425602-2 2010 Biotransformation of tamoxifen to the potent antiestrogen endoxifen is performed by cytochrome P450 (CYP) enzymes, in particular the CYP2D6 isoform. Tamoxifen 21-30 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 133-139 20425602-8 2010 This review summarizes the literature to date with a focus on clinically relevant recent studies that examined the association between CYP2D6 polymorphisms and tamoxifen-associated outcomes. Tamoxifen 160-169 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 135-141 19812351-9 2010 Constitutive expression of the tamoxifen-metabolizing enzymes CYP1B1, CYP2A6, CYP2B6, CYP2C8/9/19, CYP2D6, and SULT2A1 in glandular and surface epithelia was shown, but there was a large interindividual variation. Tamoxifen 31-40 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 99-105 19189210-0 2010 Impact of CYP2D6 polymorphisms in tamoxifen adjuvant breast cancer treatment. Tamoxifen 34-43 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 10-16 19189210-1 2010 The aim of this study is to evaluate the impact of CYP2D6 genotyping in predicting disease-free survival and toxicity in breast cancer patients treated with adjuvant tamoxifen. Tamoxifen 166-175 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 51-57 19189210-7 2010 In breast cancer, patients treated with adjuvant tamoxifen, non-functional and severely impaired CYP2D6 variants are associated with a worse DFS and with a higher frequency of severe and mild toxicities. Tamoxifen 49-58 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 97-103 21152245-9 2010 Strong correlations between allelic variation in the tamoxifen pathway at CYP1A1-CYP3A4, CYP3A4-CYP2C9, and CYP2C9-SULT1A2, in addition to CYP2D6 and its adjacent genes, were seen in the placebo-arm but not the tamoxifen-arm. Tamoxifen 53-62 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 139-145 21152245-10 2010 In conclusion, beyond reinforcing a role for CYP2D6 in tamoxifen response, our pathway analysis strongly suggests that specific combinations of allelic variants in other genes make major contributions to the tamoxifen-resistance phenotype. Tamoxifen 208-217 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 45-51 19942839-13 2009 Polymorphisms in genes coding for tamoxifen metabolizing enzymes, as for instance, the CYP2D6 genotype, have the potential of becoming clinically useful predictive marker for tamoxifen response. Tamoxifen 34-43 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 87-93 23226048-6 2010 The pharmacological activity of tamoxifen depends on its conversion by cytochrome P450 2D6 (CYP2D6) to its abundant active metabolite, endoxifen. Tamoxifen 32-41 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 71-90 23226048-6 2010 The pharmacological activity of tamoxifen depends on its conversion by cytochrome P450 2D6 (CYP2D6) to its abundant active metabolite, endoxifen. Tamoxifen 32-41 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 92-98 23226048-7 2010 Patients with reduced CYP2D6 activity, as a result of either their genotype or induction by the coadministration of other drugs that inhibit CYP2D6 function, produce little endoxifen and hence derive limited therapeutic benefit from tamoxifen; the same can be said about the different classes of therapeutics in breast cancer. Tamoxifen 233-242 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 22-28 20141708-0 2009 Interactions between tamoxifen and antidepressants via cytochrome P450 2D6. Tamoxifen 21-30 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 55-74 20141708-2 2009 Recent evidence suggested that some antidepressants inhibit the metabolism of tamoxifen to its more active metabolites by the cytochrome P450 2D6 (CYP2D6) enzyme, thereby decreasing the anticancer effect. Tamoxifen 78-87 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 126-145 20141708-2 2009 Recent evidence suggested that some antidepressants inhibit the metabolism of tamoxifen to its more active metabolites by the cytochrome P450 2D6 (CYP2D6) enzyme, thereby decreasing the anticancer effect. Tamoxifen 78-87 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 147-153 20141708-3 2009 This article reviews the literature on the interactions between newer antidepressants and tamoxifen via CYP2D6 and offers treatment recommendations. Tamoxifen 90-99 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 104-110 19942839-13 2009 Polymorphisms in genes coding for tamoxifen metabolizing enzymes, as for instance, the CYP2D6 genotype, have the potential of becoming clinically useful predictive marker for tamoxifen response. Tamoxifen 175-184 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 87-93 19189212-0 2009 The CYP2D6*4 polymorphism affects breast cancer survival in tamoxifen users. Tamoxifen 60-69 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 4-10 20120834-3 2009 One area of particular interest is the impact of cytochrome P450 CYP2D6 genetic polymorphisms on tamoxifen metabolism. Tamoxifen 97-106 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 65-71 20120834-12 2009 Anticipated data from retrospective analysis of large adjuvant randomized trials of tamoxifen should help address the clinical utility of CYP2D6 testing. Tamoxifen 84-93 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 138-144 19189212-1 2009 Cytochrome P450 2D6 (CYP2D6) plays an important role in the formation of endoxifen, the active metabolite of tamoxifen. Tamoxifen 109-118 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-19 19189212-1 2009 Cytochrome P450 2D6 (CYP2D6) plays an important role in the formation of endoxifen, the active metabolite of tamoxifen. Tamoxifen 109-118 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 21-27 19189212-2 2009 In this study the association between the most prevalent CYP2D6 null-allele in Caucasians (CYP2D6*4) and breast cancer mortality was examined among all incident users of tamoxifen in a population-based cohort study. Tamoxifen 170-179 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 57-63 19189212-2 2009 In this study the association between the most prevalent CYP2D6 null-allele in Caucasians (CYP2D6*4) and breast cancer mortality was examined among all incident users of tamoxifen in a population-based cohort study. Tamoxifen 170-179 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 91-97 19189212-6 2009 The risk of breast cancer mortality is increased in tamoxifen users with decreased CYP2D6 activity, consistent with the model in which endoxifen formation is dependent on CYP2D6 activity. Tamoxifen 52-61 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 83-89 19189212-6 2009 The risk of breast cancer mortality is increased in tamoxifen users with decreased CYP2D6 activity, consistent with the model in which endoxifen formation is dependent on CYP2D6 activity. Tamoxifen 52-61 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 171-177 19914545-6 2009 The other gene that will be discussed in the review is cytochrome P450 2D6 (CYP2D6; gene: CYP2D6), which has many genetic variants that impair the bioactivation and effectiveness of tamoxifen therapy. Tamoxifen 182-191 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 55-74 19153830-0 2009 Association between CYP2D6 genotype and tamoxifen-induced hot flashes in a prospective cohort. Tamoxifen 40-49 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 20-26 19153830-1 2009 Women with reduced CYP2D6 activity have low endoxifen concentrations and likely worse long term benefits from tamoxifen. Tamoxifen 110-119 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 19-25 19153830-2 2009 We investigated the association between CYP2D6 genotype and tamoxifen-induced hot flashes in a prospective cohort. Tamoxifen 60-69 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 40-46 19153830-7 2009 CYP2D6 activity may be a modest predictive factor for tamoxifen-induced hot flashes. Tamoxifen 54-63 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 19809024-0 2009 Association between CYP2D6 polymorphisms and outcomes among women with early stage breast cancer treated with tamoxifen. Tamoxifen 110-119 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 20-26 19809024-3 2009 OBJECTIVE: To determine whether CYP2D6 variation is associated with clinical outcomes in women receiving adjuvant tamoxifen. Tamoxifen 114-123 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 32-38 19809024-14 2009 CONCLUSION: Among women with breast cancer treated with tamoxifen, there was an association between CYP2D6 variation and clinical outcomes, such that the presence of 2 functional CYP2D6 alleles was associated with better clinical outcomes and the presence of nonfunctional or reduced-function alleles with worse outcomes. Tamoxifen 56-65 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 100-106 19809024-14 2009 CONCLUSION: Among women with breast cancer treated with tamoxifen, there was an association between CYP2D6 variation and clinical outcomes, such that the presence of 2 functional CYP2D6 alleles was associated with better clinical outcomes and the presence of nonfunctional or reduced-function alleles with worse outcomes. Tamoxifen 56-65 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 179-185 19914545-6 2009 The other gene that will be discussed in the review is cytochrome P450 2D6 (CYP2D6; gene: CYP2D6), which has many genetic variants that impair the bioactivation and effectiveness of tamoxifen therapy. Tamoxifen 182-191 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 76-82 19914545-6 2009 The other gene that will be discussed in the review is cytochrome P450 2D6 (CYP2D6; gene: CYP2D6), which has many genetic variants that impair the bioactivation and effectiveness of tamoxifen therapy. Tamoxifen 182-191 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 90-96 19592233-4 2009 There is now considerable mechanistic, pharmacologic and clinical pharmacogenetic evidence in support of the notion that CYP2D6 genetic variants and phenocopying effects through drug interaction by CYP2D6 inhibitors influence plasma concentrations of active tamoxifen metabolites and negatively impact tamoxifen outcome. Tamoxifen 258-267 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 121-127 19574470-4 2009 The polymorphic CYP2D6 is the key enzyme in this biotransformation, and recent mechanistic, pharmacologic, and clinical evidence suggests that genetic variants and drug interaction by CYP2D6 inhibitors influence the plasma concentrations of active tamoxifen metabolites and the outcomes of tamoxifen-treated patients. Tamoxifen 248-257 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 16-22 19574470-4 2009 The polymorphic CYP2D6 is the key enzyme in this biotransformation, and recent mechanistic, pharmacologic, and clinical evidence suggests that genetic variants and drug interaction by CYP2D6 inhibitors influence the plasma concentrations of active tamoxifen metabolites and the outcomes of tamoxifen-treated patients. Tamoxifen 248-257 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 184-190 19574470-4 2009 The polymorphic CYP2D6 is the key enzyme in this biotransformation, and recent mechanistic, pharmacologic, and clinical evidence suggests that genetic variants and drug interaction by CYP2D6 inhibitors influence the plasma concentrations of active tamoxifen metabolites and the outcomes of tamoxifen-treated patients. Tamoxifen 290-299 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 16-22 19574470-4 2009 The polymorphic CYP2D6 is the key enzyme in this biotransformation, and recent mechanistic, pharmacologic, and clinical evidence suggests that genetic variants and drug interaction by CYP2D6 inhibitors influence the plasma concentrations of active tamoxifen metabolites and the outcomes of tamoxifen-treated patients. Tamoxifen 290-299 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 184-190 19596663-1 2009 OBJECTIVE: The CYP2D6 enzyme plays a major role in converting tamoxifen to its active metabolites. Tamoxifen 62-71 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 15-21 19596663-3 2009 METHODS: CYP2D6 genotyping was performed in 154 node-negative breast cancer patients who had received adjuvant tamoxifen treatment alone. Tamoxifen 111-120 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 9-15 19690182-11 2009 Together, these results provide evidence for a null association between drug-compromised CYP2D6 activity and breast cancer recurrence among tamoxifen-treated women. Tamoxifen 140-149 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 89-95 19592233-4 2009 There is now considerable mechanistic, pharmacologic and clinical pharmacogenetic evidence in support of the notion that CYP2D6 genetic variants and phenocopying effects through drug interaction by CYP2D6 inhibitors influence plasma concentrations of active tamoxifen metabolites and negatively impact tamoxifen outcome. Tamoxifen 258-267 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 198-204 19592233-4 2009 There is now considerable mechanistic, pharmacologic and clinical pharmacogenetic evidence in support of the notion that CYP2D6 genetic variants and phenocopying effects through drug interaction by CYP2D6 inhibitors influence plasma concentrations of active tamoxifen metabolites and negatively impact tamoxifen outcome. Tamoxifen 302-311 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 121-127 19592233-4 2009 There is now considerable mechanistic, pharmacologic and clinical pharmacogenetic evidence in support of the notion that CYP2D6 genetic variants and phenocopying effects through drug interaction by CYP2D6 inhibitors influence plasma concentrations of active tamoxifen metabolites and negatively impact tamoxifen outcome. Tamoxifen 302-311 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 198-204 19592233-6 2009 Therefore, in the future, a personalised approach for an optimal tamoxifen benefit should consider a CYP2D6 genotype guided adjuvant endocrine treatment strategy and avoid non-adherence as well as strong CYP2D6 inhibitors such as co-medications. Tamoxifen 65-74 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 101-107 19592233-6 2009 Therefore, in the future, a personalised approach for an optimal tamoxifen benefit should consider a CYP2D6 genotype guided adjuvant endocrine treatment strategy and avoid non-adherence as well as strong CYP2D6 inhibitors such as co-medications. Tamoxifen 65-74 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 204-210 19644023-3 2009 Tamoxifen therapeutic failure in breast cancer has been associated with reduced CYP2D6 activity due to inefficient activation of tamoxifen. Tamoxifen 0-9 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 80-86 19644023-3 2009 Tamoxifen therapeutic failure in breast cancer has been associated with reduced CYP2D6 activity due to inefficient activation of tamoxifen. Tamoxifen 129-138 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 80-86 19647203-3 2009 Recently, it has been suggested that patients with inherited non-functional alleles of the cytochrome P450 CYP2D6 might be poor candidates for adjuvant tamoxifen therapy, because women with these variant alleles have reduced concentrations of the tamoxifen metabolites that most strongly bind the oestrogen receptor. Tamoxifen 152-161 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 107-113 19647203-3 2009 Recently, it has been suggested that patients with inherited non-functional alleles of the cytochrome P450 CYP2D6 might be poor candidates for adjuvant tamoxifen therapy, because women with these variant alleles have reduced concentrations of the tamoxifen metabolites that most strongly bind the oestrogen receptor. Tamoxifen 247-256 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 107-113 19647203-5 2009 However, dose-setting studies with clinical and biomarker outcomes, studies associating clinical outcomes with serum concentrations of tamoxifen and its metabolites, and a simple model of receptor binding, all suggest that tamoxifen and its metabolites should reach concentrations sufficient to achieve the therapeutic effect regardless of CYP2D6 inhibition. Tamoxifen 223-232 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 340-346 19398943-6 2009 Cytochrome P450 (CYP) 2D6 encodes for a liver enzyme that is responsible for the conversion of tamoxifen into its active metabolite, endoxifen. Tamoxifen 95-104 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-25 19629072-2 2009 The pharmacological activity of tamoxifen is dependent on its conversion by the hepatic drug-metabolizing enzyme cytochrome P450 2D6 (CYP2D6) to its abundant metabolite, endoxifen. Tamoxifen 32-41 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 113-132 19629072-2 2009 The pharmacological activity of tamoxifen is dependent on its conversion by the hepatic drug-metabolizing enzyme cytochrome P450 2D6 (CYP2D6) to its abundant metabolite, endoxifen. Tamoxifen 32-41 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 134-140 19629072-3 2009 Patients with reduced CYP2D6 activity, as a result of either their genotype or induction by the co-administration of drugs that inhibit CYP2D6 function, produce little endoxifen and seem to derive inferior therapeutic benefit from tamoxifen. Tamoxifen 231-240 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 22-28 19421167-0 2009 Cytochrome P450 2D6 activity predicts discontinuation of tamoxifen therapy in breast cancer patients. Tamoxifen 57-66 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-19 19421167-3 2009 We hypothesized that polymorphisms in CYP2D6, the enzyme responsible for tamoxifen activation, predict for tamoxifen discontinuation. Tamoxifen 73-82 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 38-44 19421167-3 2009 We hypothesized that polymorphisms in CYP2D6, the enzyme responsible for tamoxifen activation, predict for tamoxifen discontinuation. Tamoxifen 107-116 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 38-44 19421167-4 2009 Tamoxifen-treated women (n=297) were genotyped for CYP2D6 variants and assigned a "score" based on predicted allele activities from 0 (no activity) to 2 (high activity). Tamoxifen 0-9 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 51-57 19421167-7 2009 These data suggest that presence of active CYP2D6 alleles may predict for higher likelihood of tamoxifen discontinuation. Tamoxifen 95-104 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 43-49 19244106-2 2009 Tamoxifen is extensively metabolized by cytochrome P450 enzymes, and recent in vivo studies have shown that women with genetically impaired cytochrome P450 2D6 have reduced production of endoxifen and a higher risk of breast cancer recurrence. Tamoxifen 0-9 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 140-159 19398943-7 2009 Variant alleles in CYP2D6 or the use of medications that inhibit the enzyme clearly influence tamoxifen"s metabolism into endoxifen. Tamoxifen 94-103 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 19-25 19398943-9 2009 In this review, we will summarize recent data that examined associations between CYP2D6 activity and effects on tamoxifen"s metabolism and efficacy. Tamoxifen 112-121 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 81-87 19118028-0 2009 Clinical implications of CYP2D6 genotyping in tamoxifen treatment for breast cancer. Tamoxifen 46-55 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 25-31 19200418-2 2009 Tamoxifen is biotransformed to the potent antiestrogen endoxifen almost exclusively through the cytochrome P450 (CYP) 2D6 isoform. Tamoxifen 0-9 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 96-121 19200418-3 2009 Although prospective data are lacking, the balance of evidence available currently suggests that a single nucleotide polymorphism in the CYP2D6 gene, particularly the presence of 2 null alleles, predicts for reduced tamoxifen metabolism and possibly poorer outcome than expected in patients with a wild-type genotype. Tamoxifen 216-225 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 137-143 19200418-4 2009 Studies evaluating the impact of genetic polymorphisms that result in CYP2D6 with reduced or no activity on long-term outcome have been mostly retrospective and conducted on archival tissues or those obtained previously in prospective studies of tamoxifen. Tamoxifen 246-255 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 70-76 19118028-1 2009 In October 2006 the Food and Drug Administration recommended an update in the tamoxifen label to reflect the increased risk of recurrence in breast cancer patients who are cytochrome P450 2D6 (CYP2D6) poor metabolizers. Tamoxifen 78-87 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 172-191 19118028-1 2009 In October 2006 the Food and Drug Administration recommended an update in the tamoxifen label to reflect the increased risk of recurrence in breast cancer patients who are cytochrome P450 2D6 (CYP2D6) poor metabolizers. Tamoxifen 78-87 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 193-199 19118028-3 2009 More clinical studies addressing the relation between the CYP2D6 genotype and tamoxifen efficacy have been published since, mostly describing Caucasian populations in the adjuvant treatment setting. Tamoxifen 78-87 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 58-64 19118028-5 2009 Furthermore, the possibility to implement CYP2D6 genotyping in clinical practice is evaluated by analyzing the results of six studies on mainly Caucasian patients using adjuvant tamoxifen. Tamoxifen 178-187 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 42-48 19902987-15 2009 Because of the important role of CYP2D6 in tamoxifen metabolism and activation, PMs are likely to exhibit therapeutic failure, and ultrarapid metabolizers (UMs) are likely to experience adverse effects and toxicities. Tamoxifen 43-52 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 33-39 19902987-17 2009 Tamoxifen-treated cancer patients carrying CYP2D6*4, *5, *10, or *41 associated with significantly decreased formation of antiestrogenic metabolites had significantly more recurrences of breast cancer and shorter relapse-free periods. Tamoxifen 0-9 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 43-49 19902987-18 2009 Many studies have identified the genetic CYP2D6 status as an independent predictor of the outcome of tamoxifen treatment in women with breast cancer, but others have not observed this relationship. Tamoxifen 101-110 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 41-47 19902987-19 2009 Thus, more favourable tamoxifen treatment seems to be feasible through a priori genetic assessment of CYP2D6, and proper dose adjustment may be needed when the CYP2D6 genotype is determined in a patient. Tamoxifen 22-31 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 102-108 19019258-0 2008 Pharmacogenetics and breast cancer endocrine therapy: CYP2D6 as a predictive factor for tamoxifen metabolism and drug response? Tamoxifen 88-97 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 54-60 19088019-2 2008 Polymorphisms of CYP2D6 in particular have been associated with effects on tamoxifen disposition and clinical efficacy, with interethnic differences in distribution of functional alleles that affect metabolizer phenotype. Tamoxifen 75-84 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 17-23 19047159-9 2008 A combined analysis with the data of the known tamoxifen predictor CYP2D6 showed an improvement of outcome prediction compared with CYP2D6 or TC21 genotype status alone (per mutated gene HR, 2.35; 95% CI, 1.34-4.14). Tamoxifen 47-56 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 67-73 19059062-4 2008 Reduced cytochrome P450 (CYP) 2D6 activity leads to therapeutic failure of tamoxifen in the prevention and treatment of breast cancer, as a result of absence of conversion of the prodrug to its active forms. Tamoxifen 75-84 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 8-33 19019258-3 2008 Cytochrome P450 2D6 (CYP2D6) is crucial in the metabolism of tamoxifen to its active metabolite endoxifen. Tamoxifen 61-70 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-19 19019258-3 2008 Cytochrome P450 2D6 (CYP2D6) is crucial in the metabolism of tamoxifen to its active metabolite endoxifen. Tamoxifen 61-70 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 21-27 19019258-4 2008 Women with genetic variants of CYP2D6 or who take drugs that inhibit the enzyme have low endoxifen plasma concentrations and may show reduced benefits to tamoxifen treatment. Tamoxifen 154-163 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 31-37 19019258-5 2008 CYP2D6 polymorphisms and variants in other candidate genes may also influence secondary benefits and side effects of tamoxifen. Tamoxifen 117-126 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 19019258-6 2008 Here, we summarise data suggesting that CYP2D6 status may be an important predictor of the benefits of tamoxifen to an individual; in addition, we briefly discuss the role of variants in other candidate genes. Tamoxifen 103-112 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 40-46 19019258-7 2008 Whether CYP2D6 status should be determined prior to initiating tamoxifen therapy is currently under debate and may be appropriate only for select women who are candidates for tamoxifen alone but for whom alternative standard options are available. Tamoxifen 175-184 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 8-14 18794098-0 2008 Cytochrome P450 2D6 and homeobox 13/interleukin-17B receptor: combining inherited and tumor gene markers for prediction of tamoxifen resistance. Tamoxifen 123-132 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-19 18794105-10 2008 Prospective studies should be undertaken to establish the effect of CYP2D6 status on outcome in familial breast cancer patients treated with tamoxifen. Tamoxifen 141-150 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 68-74 19194367-2 2008 Tamoxifen is metabolized to its more active form by cytochrome P450 2D6 (CYP2D6); decreases in CYP2D6 activity, either by inactivating polymorphisms or drug interactions, can reduce concentrations of tamoxifen"s active metabolites. Tamoxifen 0-9 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 52-71 19194367-2 2008 Tamoxifen is metabolized to its more active form by cytochrome P450 2D6 (CYP2D6); decreases in CYP2D6 activity, either by inactivating polymorphisms or drug interactions, can reduce concentrations of tamoxifen"s active metabolites. Tamoxifen 0-9 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 73-79 19194367-2 2008 Tamoxifen is metabolized to its more active form by cytochrome P450 2D6 (CYP2D6); decreases in CYP2D6 activity, either by inactivating polymorphisms or drug interactions, can reduce concentrations of tamoxifen"s active metabolites. Tamoxifen 0-9 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 95-101 19194367-2 2008 Tamoxifen is metabolized to its more active form by cytochrome P450 2D6 (CYP2D6); decreases in CYP2D6 activity, either by inactivating polymorphisms or drug interactions, can reduce concentrations of tamoxifen"s active metabolites. Tamoxifen 200-209 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 52-71 19194367-2 2008 Tamoxifen is metabolized to its more active form by cytochrome P450 2D6 (CYP2D6); decreases in CYP2D6 activity, either by inactivating polymorphisms or drug interactions, can reduce concentrations of tamoxifen"s active metabolites. Tamoxifen 200-209 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 73-79 19194367-2 2008 Tamoxifen is metabolized to its more active form by cytochrome P450 2D6 (CYP2D6); decreases in CYP2D6 activity, either by inactivating polymorphisms or drug interactions, can reduce concentrations of tamoxifen"s active metabolites. Tamoxifen 200-209 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 95-101 19194367-3 2008 Clinical studies demonstrate that breast cancer patients treated with adjuvant tamoxifen who have decreased CYP2D6 due to genetic polymorphisms or drug interactions may have an increased risk of recurrence and reductions in disease-free survival. Tamoxifen 79-88 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 108-114 18794098-1 2008 PURPOSE: Genetic variation in cytochrome P450 2D6 (CYP2D6) and the gene expression ratio of the homeobox 13 (HOXB13) to interleukin-17B receptor (IL17BR) are associated with tamoxifen resistance. Tamoxifen 174-183 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 30-49 18794098-1 2008 PURPOSE: Genetic variation in cytochrome P450 2D6 (CYP2D6) and the gene expression ratio of the homeobox 13 (HOXB13) to interleukin-17B receptor (IL17BR) are associated with tamoxifen resistance. Tamoxifen 174-183 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 51-57 18794098-2 2008 We sought to determine the combined effect of inherited (CYP2D6) and somatic (HOXB13/IL17BR) gene variation in tamoxifen-treated breast cancer. Tamoxifen 111-120 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 57-63 18794098-11 2008 CONCLUSIONS: An index composed of inherited (CYP2D6) and tumor (HOXB13/IL17BR) gene variation identifies patients with varying degrees of resistance to tamoxifen. Tamoxifen 152-161 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 45-51 18794105-2 2008 Conversion of tamoxifen to its active metabolite, endoxifen, is reduced by low activity of the cytochrome P450 enzyme, CYP2D6. Tamoxifen 14-23 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 119-125 18794105-3 2008 We examined the effect of reduced CYP2D6 activity on the response to tamoxifen in patients with familial early-onset breast cancer. Tamoxifen 69-78 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 34-40 18754887-0 2008 Comment on "Impact of CYP2D6*10 on recurrence-free survival in breast cancer patients receiving adjuvant tamoxifen therapy". Tamoxifen 105-114 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 22-28 18407954-0 2008 Association between CYP2D6 *10 genotype and survival of breast cancer patients receiving tamoxifen treatment. Tamoxifen 89-98 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 20-26 18407954-1 2008 BACKGROUND: Human cytochrome P450 2D6 (CYP2D6) genotype may affect the efficacy of tamoxifen treatment in Caucasian women with breast cancer. Tamoxifen 83-92 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 18-37 18407954-1 2008 BACKGROUND: Human cytochrome P450 2D6 (CYP2D6) genotype may affect the efficacy of tamoxifen treatment in Caucasian women with breast cancer. Tamoxifen 83-92 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 39-45 18407954-8 2008 CONCLUSION: In tamoxifen-treated patients, women with the CYP2D6 *10 T/T genotype have a lower 4OHtam level in the serum and a worse clinical outcome. Tamoxifen 15-24 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 58-64 18445827-2 2008 This difference could be due to differences in tamoxifen metabolism because levels of endoxifen, the active tamoxifen metabolite, vary with the number of mutant alleles, including the *4 allele, of the gene encoding cytochrome P450 2D6 (CYP2D6). Tamoxifen 47-56 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 216-235 18445827-2 2008 This difference could be due to differences in tamoxifen metabolism because levels of endoxifen, the active tamoxifen metabolite, vary with the number of mutant alleles, including the *4 allele, of the gene encoding cytochrome P450 2D6 (CYP2D6). Tamoxifen 47-56 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 237-243 18445827-2 2008 This difference could be due to differences in tamoxifen metabolism because levels of endoxifen, the active tamoxifen metabolite, vary with the number of mutant alleles, including the *4 allele, of the gene encoding cytochrome P450 2D6 (CYP2D6). Tamoxifen 108-117 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 216-235 18445827-9 2008 CONCLUSIONS: Modeling suggests that among patients who are wild type for CYP2D6, 5-year disease-free survival outcomes are similar to or perhaps even superior with tamoxifen than with aromatase inhibitors. Tamoxifen 164-173 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 73-79 17541741-1 2008 We utilized data from the comparison group of the Women"s Healthy Eating and Living randomized trial to investigate an "a priori" hypothesis suggested by CYP2D6 studies that hot flashes may be an independent predictor of tamoxifen efficacy. Tamoxifen 221-230 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 154-160 18294285-0 2008 Impact of CYP2D6*10 on recurrence-free survival in breast cancer patients receiving adjuvant tamoxifen therapy. Tamoxifen 93-102 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 10-16 18294285-1 2008 The clinical outcomes of breast cancer patients treated with tamoxifen may be influenced by the activity of cytochrome P450 2D6 (CYP2D6) enzyme because tamixifen is metabolized by CYP2D6 to its active forms of antiestrogenic metabolite, 4-hydroxytamoxifen and endoxifen. Tamoxifen 61-70 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 108-127 18294285-1 2008 The clinical outcomes of breast cancer patients treated with tamoxifen may be influenced by the activity of cytochrome P450 2D6 (CYP2D6) enzyme because tamixifen is metabolized by CYP2D6 to its active forms of antiestrogenic metabolite, 4-hydroxytamoxifen and endoxifen. Tamoxifen 61-70 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 129-135 18294285-1 2008 The clinical outcomes of breast cancer patients treated with tamoxifen may be influenced by the activity of cytochrome P450 2D6 (CYP2D6) enzyme because tamixifen is metabolized by CYP2D6 to its active forms of antiestrogenic metabolite, 4-hydroxytamoxifen and endoxifen. Tamoxifen 61-70 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 180-186 18294285-2 2008 We investigated the predictive value of the CYP2D6*10 allele, which decreased CYP2D6 activity, for clinical outcomes of patients that received adjuvant tamoxifen monotherapy after surgical operation on breast cancer. Tamoxifen 152-161 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 44-50 17713466-2 2008 As part of a multicenter prospective observational trial in 176 breast cancer patients, we tested the hypothesis that tamoxifen-induced lipid changes were associated with genetic variants in candidate target genes (CYP2D6, ESR1, and ESR2). Tamoxifen 118-127 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 215-221 18663817-0 2008 CYP2D6 pharmacogenomics of tamoxifen treatment. Tamoxifen 27-36 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 18202689-3 2008 In other fields of drug therapy, such as for breast cancer, CYP2D6 status has been reported to be an independent predictor for the outcome with tamoxifen. Tamoxifen 144-153 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 60-66 18072234-6 2008 CYP2D6 plays a central role in the metabolism to endoxifen and 1 published study shows that genotypic differences in CYP2D6 and use of CYP2D6 inhibitors has an impact on outcomes of women treated with tamoxifen. Tamoxifen 201-210 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 18072234-6 2008 CYP2D6 plays a central role in the metabolism to endoxifen and 1 published study shows that genotypic differences in CYP2D6 and use of CYP2D6 inhibitors has an impact on outcomes of women treated with tamoxifen. Tamoxifen 201-210 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 117-123 18072234-6 2008 CYP2D6 plays a central role in the metabolism to endoxifen and 1 published study shows that genotypic differences in CYP2D6 and use of CYP2D6 inhibitors has an impact on outcomes of women treated with tamoxifen. Tamoxifen 201-210 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 117-123 18202689-4 2008 Thus, a more favorable tamoxifen treatment seems to be feasible through a priori genetic assessment of CYP2D6. Tamoxifen 23-32 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 103-109 18637494-4 2008 Tamoxifen requires "metabolic activation" catalyzed by cytochrome P450 2D6 (CYP2D6) to form hydroxylated metabolites-4-hydroxytamoxifen and endoxifen (N-desmethyl-4-hydroxytamoxifen)-both of which are much more potent than is the parent drug. Tamoxifen 0-9 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 55-74 18279059-7 2008 We review the study by Schroth and colleagues, evaluating the correlation between genotype for CYP2D6 and other enzymes involved in tamoxifen metabolism and breast cancer outcome. Tamoxifen 132-141 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 95-101 18637494-4 2008 Tamoxifen requires "metabolic activation" catalyzed by cytochrome P450 2D6 (CYP2D6) to form hydroxylated metabolites-4-hydroxytamoxifen and endoxifen (N-desmethyl-4-hydroxytamoxifen)-both of which are much more potent than is the parent drug. Tamoxifen 0-9 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 76-82 17947222-2 2008 Clinical studies indicate that CYP2D6 and SULT1A1 genotypes are predictors for treatment response to tamoxifen. Tamoxifen 101-110 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 31-37 17947222-9 2008 CONCLUSION: CYP2D6 and SULT1A1 genotypes may partly explain the wide inter-individual variations in the serum levels of tamoxifen and its metabolites. Tamoxifen 120-129 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 12-18 20824020-0 2008 Clinical Relevance of CYP2D6 Genetics for Tamoxifen Response in Breast Cancer. Tamoxifen 42-51 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 22-28 20824020-3 2008 CYP2D6 is the key enzyme in this biotransformation, and recent mechanistic, pharmacologic, and clinical pharmacogenetic evidence suggests that genetic variants and drug interaction by CYP2D6 inhibitors influence plasma concentrations of active tamoxifen metabolites and outcome of patients treated with adjuvant tamoxifen. Tamoxifen 244-253 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 20824020-3 2008 CYP2D6 is the key enzyme in this biotransformation, and recent mechanistic, pharmacologic, and clinical pharmacogenetic evidence suggests that genetic variants and drug interaction by CYP2D6 inhibitors influence plasma concentrations of active tamoxifen metabolites and outcome of patients treated with adjuvant tamoxifen. Tamoxifen 244-253 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 184-190 20824020-3 2008 CYP2D6 is the key enzyme in this biotransformation, and recent mechanistic, pharmacologic, and clinical pharmacogenetic evidence suggests that genetic variants and drug interaction by CYP2D6 inhibitors influence plasma concentrations of active tamoxifen metabolites and outcome of patients treated with adjuvant tamoxifen. Tamoxifen 312-321 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 20824020-3 2008 CYP2D6 is the key enzyme in this biotransformation, and recent mechanistic, pharmacologic, and clinical pharmacogenetic evidence suggests that genetic variants and drug interaction by CYP2D6 inhibitors influence plasma concentrations of active tamoxifen metabolites and outcome of patients treated with adjuvant tamoxifen. Tamoxifen 312-321 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 184-190 17765940-3 2007 The metabolite is formed through the enzymatic product of CYP2D6 which also interacts with specific selective serotonin reuptake inhibitors (SSRIs) used to prevent the hot flashes observed in up to 45% of patients taking tamoxifen. Tamoxifen 221-230 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 58-64 18445989-4 2008 CYP2D6 and CYP3A4 are major contributors to the metabolism of tamoxifen. Tamoxifen 62-71 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 17882159-0 2008 Tamoxifen pharmacogenomics: the role of CYP2D6 as a predictor of drug response. Tamoxifen 0-9 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 40-46 17882159-3 2008 CYP2D6 is the rate-limiting enzyme catalyzing the conversion of tamoxifen into metabolites with significantly greater affinity for the ER and greater ability to inhibit cell proliferation. Tamoxifen 64-73 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 17882159-4 2008 Both genetic and environmental (drug-induced) factors that alter CYP2D6 enzyme activity directly affect the concentrations of the active tamoxifen metabolites and the outcomes of patients receiving adjuvant tamoxifen. Tamoxifen 137-146 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 65-71 17882159-4 2008 Both genetic and environmental (drug-induced) factors that alter CYP2D6 enzyme activity directly affect the concentrations of the active tamoxifen metabolites and the outcomes of patients receiving adjuvant tamoxifen. Tamoxifen 207-216 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 65-71 18024866-2 2007 We investigated the predictive value of genetic variants of CYP2D6, CYP2C19, and three other cytochrome P450 enzymes for tamoxifen treatment outcome. Tamoxifen 121-130 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 60-66 18024866-7 2007 CONCLUSION: Because genetically determined, impaired tamoxifen metabolism results in worse treatment outcomes, genotyping for CYP2D6 alleles *4, *5, *10, and *41 can identify patients who will have little benefit from adjuvant tamoxifen therapy. Tamoxifen 53-62 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 126-132 18024866-7 2007 CONCLUSION: Because genetically determined, impaired tamoxifen metabolism results in worse treatment outcomes, genotyping for CYP2D6 alleles *4, *5, *10, and *41 can identify patients who will have little benefit from adjuvant tamoxifen therapy. Tamoxifen 227-236 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 126-132 17518364-5 2007 Tamoxifen has been shown to be metabolized by CYP2D6 to the more potent metabolite endoxifen. Tamoxifen 0-9 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 46-52 17761971-0 2007 Clinical implications of CYP2D6 genotypes predictive of tamoxifen pharmacokinetics in metastatic breast cancer. Tamoxifen 56-65 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 25-31 17761971-1 2007 PURPOSE: The CYP3A and CYP2D6 enzymes play a major role in converting tamoxifen to its active metabolites. Tamoxifen 70-79 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 23-29 17761971-5 2007 Common alleles of CYP2D6 and PXR were identified in 202 patients treated with tamoxifen 20 mg daily for more than 8 weeks. Tamoxifen 78-87 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 18-24 17761971-10 2007 The median TTP for patients receiving tamoxifen was shorter in those carrying CYP2D6*10/*10 than for others (5.0 v 21.8 months, P = .0032) CONCLUSION: CYP2D6*10/*10 is associated with lower steady-state plasma concentrations of active tamoxifen metabolites, which could possibly influence the clinical outcome by tamoxifen in Asian breast cancer patients. Tamoxifen 38-47 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 78-84 17761971-10 2007 The median TTP for patients receiving tamoxifen was shorter in those carrying CYP2D6*10/*10 than for others (5.0 v 21.8 months, P = .0032) CONCLUSION: CYP2D6*10/*10 is associated with lower steady-state plasma concentrations of active tamoxifen metabolites, which could possibly influence the clinical outcome by tamoxifen in Asian breast cancer patients. Tamoxifen 38-47 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 151-157 17761971-10 2007 The median TTP for patients receiving tamoxifen was shorter in those carrying CYP2D6*10/*10 than for others (5.0 v 21.8 months, P = .0032) CONCLUSION: CYP2D6*10/*10 is associated with lower steady-state plasma concentrations of active tamoxifen metabolites, which could possibly influence the clinical outcome by tamoxifen in Asian breast cancer patients. Tamoxifen 235-244 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 78-84 17761971-10 2007 The median TTP for patients receiving tamoxifen was shorter in those carrying CYP2D6*10/*10 than for others (5.0 v 21.8 months, P = .0032) CONCLUSION: CYP2D6*10/*10 is associated with lower steady-state plasma concentrations of active tamoxifen metabolites, which could possibly influence the clinical outcome by tamoxifen in Asian breast cancer patients. Tamoxifen 235-244 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 151-157 17761971-10 2007 The median TTP for patients receiving tamoxifen was shorter in those carrying CYP2D6*10/*10 than for others (5.0 v 21.8 months, P = .0032) CONCLUSION: CYP2D6*10/*10 is associated with lower steady-state plasma concentrations of active tamoxifen metabolites, which could possibly influence the clinical outcome by tamoxifen in Asian breast cancer patients. Tamoxifen 235-244 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 78-84 17761971-10 2007 The median TTP for patients receiving tamoxifen was shorter in those carrying CYP2D6*10/*10 than for others (5.0 v 21.8 months, P = .0032) CONCLUSION: CYP2D6*10/*10 is associated with lower steady-state plasma concentrations of active tamoxifen metabolites, which could possibly influence the clinical outcome by tamoxifen in Asian breast cancer patients. Tamoxifen 235-244 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 151-157 17518364-7 2007 Here, we will provide an overview of the history and application of CYP2D6 pharmacogenetics, and will discuss the clinical implications of recent developments relating to the involvement of CYP2D6 in tamoxifen treatment. Tamoxifen 200-209 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 190-196 17245346-0 2007 Can tamoxifen therapy be optimized for patients with breast cancer on the basis of CYP2D6 activity assessments? Tamoxifen 4-13 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 83-89 17244352-11 2007 The significantly improved RFS with prolonged tamoxifen treatment in CYP3A5*3 homozygotes was also seen in a multivariate Cox model (HR = 0.13, CI = 0.02 to 0.86, P = 0.03), whereas no differences could be seen for CYP2D6, SULT1A1 and UGT2B15. Tamoxifen 46-55 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 215-221 17433116-0 2007 The ethics of CYP2D6 testing for patients considering tamoxifen. Tamoxifen 54-63 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 14-20 16550168-6 2006 This includes also some anticancer drugs like tamoxifen and cyclophosphamide metabolized by CYP2D6, CYP2C19 and CYP2B6. Tamoxifen 46-55 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 92-98 17433116-1 2007 The CYP2D6 gene is responsible for the majority of tamoxifen metabolism. Tamoxifen 51-60 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 4-10 16877740-0 2006 Polymorphism in the CYP2D6 tamoxifen-metabolizing gene influences clinical effect but not hot flashes: data from the Italian Tamoxifen Trial. Tamoxifen 27-36 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 20-26 16877740-0 2006 Polymorphism in the CYP2D6 tamoxifen-metabolizing gene influences clinical effect but not hot flashes: data from the Italian Tamoxifen Trial. Tamoxifen 125-134 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 20-26 16815318-0 2006 Quantitative effect of CYP2D6 genotype and inhibitors on tamoxifen metabolism: implication for optimization of breast cancer treatment. Tamoxifen 57-66 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 23-29 16815318-9 2006 CONCLUSION: CYP2D6 genotype and concomitant potent CYP2D6 inhibitors are highly associated with endoxifen plasma concentration and may have an impact on the response to tamoxifen therapy. Tamoxifen 169-178 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 12-18 16815318-9 2006 CONCLUSION: CYP2D6 genotype and concomitant potent CYP2D6 inhibitors are highly associated with endoxifen plasma concentration and may have an impact on the response to tamoxifen therapy. Tamoxifen 169-178 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 51-57 17115111-0 2007 The impact of cytochrome P450 2D6 metabolism in women receiving adjuvant tamoxifen. Tamoxifen 73-82 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 14-33 17115111-2 2007 CYP2D6 genetic variation and inhibitors of the enzyme markedly reduce endoxifen plasma concentrations in tamoxifen-treated patients. Tamoxifen 105-114 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 17115111-3 2007 Using a North Central Cancer Treatment Group adjuvant tamoxifen trial, we performed a comprehensive evaluation of CYP2D6 metabolism by assessing the combined effect of genetic variation and inhibition of the enzyme system on breast cancer recurrence and death. Tamoxifen 54-63 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 114-120 17115111-12 2007 CONCLUSION: CYP2D6 metabolism, as measured by genetic variation and enzyme inhibition, is an independent predictor of breast cancer outcome in post-menopausal women receiving tamoxifen for early breast cancer. Tamoxifen 175-184 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 12-18 17115111-13 2007 Determination of CYP2D6 genotype may be of value in selecting adjuvant hormonal therapy and it appears CYP2D6 inhibitors should be avoided in tamoxifen-treated women. Tamoxifen 142-151 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 103-109 16454691-5 2006 For example, the formation of endoxifen, which is an active metabolite of tamoxifen, was less in patients with inactive polymorphic CYP2D6 than those with the wild type enzyme. Tamoxifen 74-83 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 132-138 15632378-2 2005 Plasma concentrations of the active tamoxifen metabolite endoxifen are associated with the cytochrome P450 (CYP) 2D6 genotype. Tamoxifen 36-45 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 91-116 16267627-7 2005 At this moment, potential clinically relevant application of CYP450 pharmacogenetics for anticancer therapy may be found for CYP1A2 and flutamide, CYP2A6 and tegafur, CYP2B6 and cyclophosphamide, CYP2C8 and paclitaxel, CYP2D6 and tamoxifen, and CYP3A5. Tamoxifen 230-239 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 219-225 16771600-10 2006 Non-psychiatric drugs metabolized by CYP2D6 include metoprolol, tamoxifen, and codeine-like drugs. Tamoxifen 64-73 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 37-43 16361630-10 2005 CONCLUSION: In tamoxifen-treated patients, women with the CYP2D6 *4/*4 genotype tend to have a higher risk of disease relapse and a lower incidence of hot flashes, which is consistent with our previous observation that CYP2D6 is responsible for the metabolic activation of tamoxifen to endoxifen. Tamoxifen 15-24 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 58-64 16361630-10 2005 CONCLUSION: In tamoxifen-treated patients, women with the CYP2D6 *4/*4 genotype tend to have a higher risk of disease relapse and a lower incidence of hot flashes, which is consistent with our previous observation that CYP2D6 is responsible for the metabolic activation of tamoxifen to endoxifen. Tamoxifen 15-24 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 219-225 16361630-10 2005 CONCLUSION: In tamoxifen-treated patients, women with the CYP2D6 *4/*4 genotype tend to have a higher risk of disease relapse and a lower incidence of hot flashes, which is consistent with our previous observation that CYP2D6 is responsible for the metabolic activation of tamoxifen to endoxifen. Tamoxifen 273-282 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 58-64 16361630-10 2005 CONCLUSION: In tamoxifen-treated patients, women with the CYP2D6 *4/*4 genotype tend to have a higher risk of disease relapse and a lower incidence of hot flashes, which is consistent with our previous observation that CYP2D6 is responsible for the metabolic activation of tamoxifen to endoxifen. Tamoxifen 273-282 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 219-225 15952058-3 2005 We examined functional polymorphisms in CYP2D6, the P450 catalyzing the formation of active tamoxifen metabolites, and UGT2B15, a Phase II enzyme facilitating the elimination of active metabolite in a retrospective study of breast cancer patients. Tamoxifen 92-101 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 40-46 15632378-12 2005 CONCLUSION: Interactions between CYP2D6 polymorphisms and coadministered antidepressants and other drugs that are CYP2D6 inhibitors may be associated with altered tamoxifen activity. Tamoxifen 163-172 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 33-39 15632378-12 2005 CONCLUSION: Interactions between CYP2D6 polymorphisms and coadministered antidepressants and other drugs that are CYP2D6 inhibitors may be associated with altered tamoxifen activity. Tamoxifen 163-172 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 114-120 15159443-7 2004 TAM and its primary metabolites undergo extensive oxidation, principally by CYP3A and CYP2D6 to metabolites that exhibit a range of pharmacological effects. Tamoxifen 0-3 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 86-92 15987423-4 2005 Cytochrome P450 2D6 (CYP2D6) and sulfotransferase 1A1 (SULT1A1) are polymorphic and are involved in the metabolism of tamoxifen. Tamoxifen 118-127 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-19 15987423-4 2005 Cytochrome P450 2D6 (CYP2D6) and sulfotransferase 1A1 (SULT1A1) are polymorphic and are involved in the metabolism of tamoxifen. Tamoxifen 118-127 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 21-27 15987423-8 2005 RESULTS: Carriers of the CYP2D6*4 allele demonstrated a decreased risk of recurrence when treated with tamoxifen (relative risk = 0.28, 95% confidence interval = 0.11-0.74, P = 0.0089). Tamoxifen 103-112 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 25-31 15987423-10 2005 The combination of CYP2D6*4 and/or SULT1A1*1/*1 genotypes comprised 60% of the patients and showed a 62% decreased risk of distant recurrence with tamoxifen (relative risk = 0.38, 95% confidence interval = 0.19-0.74, P = 0.0041). Tamoxifen 147-156 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 19-25 14642736-7 2003 Incubations of tamoxifen with recombinant human cytochrome P-450s (CYPs) found that CYP2C9 and CYP2D6 produced all three of the above tamoxifen metabolites, while CYP1A1 and CYP3A4 catalyzed the formation of alpha-hydroxytamoxifen and N-desmethyltamoxifen, and CYP1A2 and CYP1B1 only formed the alpha-hydroxy metabolite. Tamoxifen 134-143 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 95-101 15286089-2 2004 Tamoxifen is metabolized to an extremely potent antiestrogen by cytochrome P450 (CYP) 2D6, 2C9, and 3A isoforms. Tamoxifen 0-9 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 64-94 14642736-7 2003 Incubations of tamoxifen with recombinant human cytochrome P-450s (CYPs) found that CYP2C9 and CYP2D6 produced all three of the above tamoxifen metabolites, while CYP1A1 and CYP3A4 catalyzed the formation of alpha-hydroxytamoxifen and N-desmethyltamoxifen, and CYP1A2 and CYP1B1 only formed the alpha-hydroxy metabolite. Tamoxifen 15-24 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 95-101 14642736-8 2003 CYP2D6 exhibited the greatest activity for the formation of all three tamoxifen metabolites. Tamoxifen 70-79 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 12769667-9 2003 CYP3A4 and CYP2D6 convert tamoxifen to N-desmethyltamoxifen. Tamoxifen 26-35 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 11-17 14652237-12 2003 In vitro, troleandomycin, an inhibitor of CYP3A4, inhibited the demethylation of tamoxifen to N-desmethyl-tamoxifen by 78% (95% CI = 65% to 91%), and quinidine, an inhibitor of CYP2D6, reduced the subsequent hydroxylation of N-desmethyl-tamoxifen to endoxifen by 79% (95% CI = 50% to 108%). Tamoxifen 81-90 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 177-183 14652237-13 2003 CONCLUSIONS: Endoxifen is an active tamoxifen metabolite that is generated via CYP3A4-mediated N-demethylation and CYP2D6-mediated hydroxylation. Tamoxifen 36-45 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 115-121 14652237-15 2003 Our data suggest that CYP2D6 genotype and drug interactions should be considered in women treated with tamoxifen. Tamoxifen 103-112 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 22-28 14678248-12 2003 Genotyping of patients with regards to CYP2B6, CYP2C9 and CYP2D6 may play a role in prediction of Z-4-OH-tam formation and, consequently, ultimate therapeutic benefit of tamoxifen treatment. Tamoxifen 170-179 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 58-64 12419838-6 2002 While CYP3A4 converted tamoxifen to N-desmethyltamoxifen (38.3 +/- 7.20 pmol/20 min/pmol CYP, n = 4), the polymorphic CYP2D6 showed the highest activity for producing this metabolite (48.6+/-1.52pmol/20 min/pmol CYP). Tamoxifen 23-32 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 118-124 12419838-7 2002 CYP2D6 was also the most active in catalysing 4-hydroxylation of tamoxifen, although an order of magnitude lower level was also detected with CYP2C19. Tamoxifen 65-74 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 12124303-7 2002 CYP2D6 was the major catalyst of 4-hydroxylation at low tamoxifen concentrations (170 +/- 20 pmol/40 min/0.2 nmol P450 using 18 microM tamoxifen), but CYP2B6 showed significant activity at high substrate concentrations (28.1 +/- 0.8 and 3.1 +/- 0.5 nmol/120 min/0.2 nmol P450 for CYP2D6 and CYP2B6, respectively, using 250 microM tamoxifen). Tamoxifen 56-65 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 12207635-1 2002 AIMS: To investigate in a large panel of 50 human liver samples the contribution of CYP2C9, CYP2D6, and CYP3A4 to the overall formation of the potent antioestrogen Z-4-hydroxy-tamoxifen, and how various genotypes affect its formation from tamoxifen. Tamoxifen 176-185 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 92-98 12124303-7 2002 CYP2D6 was the major catalyst of 4-hydroxylation at low tamoxifen concentrations (170 +/- 20 pmol/40 min/0.2 nmol P450 using 18 microM tamoxifen), but CYP2B6 showed significant activity at high substrate concentrations (28.1 +/- 0.8 and 3.1 +/- 0.5 nmol/120 min/0.2 nmol P450 for CYP2D6 and CYP2B6, respectively, using 250 microM tamoxifen). Tamoxifen 135-144 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 12124303-7 2002 CYP2D6 was the major catalyst of 4-hydroxylation at low tamoxifen concentrations (170 +/- 20 pmol/40 min/0.2 nmol P450 using 18 microM tamoxifen), but CYP2B6 showed significant activity at high substrate concentrations (28.1 +/- 0.8 and 3.1 +/- 0.5 nmol/120 min/0.2 nmol P450 for CYP2D6 and CYP2B6, respectively, using 250 microM tamoxifen). Tamoxifen 135-144 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 12124303-8 2002 These two forms also catalyzed 4"-hydroxylation (13.0 +/- 1.9 and 1.4 +/- 0.1 nmol/120 min/0.2 nmol P450, respectively, for CYP2B6 and CYP2D6 at 250 microM tamoxifen; 0.51 +/- 0.08 pmol/40 min/0.2 nmol P450 for CYP2B6 at 18 microM tamoxifen). Tamoxifen 156-165 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 135-141 12124303-8 2002 These two forms also catalyzed 4"-hydroxylation (13.0 +/- 1.9 and 1.4 +/- 0.1 nmol/120 min/0.2 nmol P450, respectively, for CYP2B6 and CYP2D6 at 250 microM tamoxifen; 0.51 +/- 0.08 pmol/40 min/0.2 nmol P450 for CYP2B6 at 18 microM tamoxifen). Tamoxifen 231-240 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 135-141 12124303-9 2002 Tamoxifen N-demethylation was mediated by CYP2D6, 1A1, 1A2, and 3A4, at low substrate concentrations, with contributions by CYP1B1, 2C9, 2C19 and 3A5 at high concentrations. Tamoxifen 0-9 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 42-48 33805613-5 2021 Inconclusive results from studies investigating whether CYP2D6 genotype is associated with tamoxifen efficacy may be due to the imprecision in using CYP2D6 genotype as a surrogate of endoxifen concentration without incorporating the influence of other genetic and clinical variables. Tamoxifen 91-100 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 56-62 8681455-3 1996 In particular, the CYP102-derived structures of CYP3A4, CYP2D6 and CYP2C9 are able to rationalize the routes of tamoxifen metabolism reported in human subjects. Tamoxifen 112-121 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 56-62 9270005-0 1997 CYP2D6 catalyzes tamoxifen 4-hydroxylation in human liver. Tamoxifen 17-26 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 9270005-11 1997 Tam metabolism by CYP2D6 coexpressed with P450 reductase in a baculovirus infected insect cell line ("supersomes") exhibited marked tam 4-hydroxylation. Tamoxifen 0-3 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 18-24 9270005-11 1997 Tam metabolism by CYP2D6 coexpressed with P450 reductase in a baculovirus infected insect cell line ("supersomes") exhibited marked tam 4-hydroxylation. Tamoxifen 132-135 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 18-24 9037249-5 1997 Three of the livers with the lowest tamoxifen 4-hydroxylation activity were from genetically poor metabolisers with respect to CYP2D6. Tamoxifen 36-45 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 127-133 9037249-7 1997 The proportion of activity inhibited by quinidine correlated positively with total microsomal tamoxifen 4-hydroxylation activity (rs = 0.89, P < 0.01), indicating a major involvement of CYP2D6 in this reaction. Tamoxifen 94-103 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 189-195 9037249-10 1997 These findings indicate that the 4-hydroxylation of tamoxifen is catalysed almost exclusively by CYPs 2D6, 2C9 and 3A4 in human liver microsomes. Tamoxifen 52-61 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 97-110 29473149-1 2018 This issue of Clinical Pharmacology & Therapeutics (CPT) includes the Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for using CYP2D6 genotyping to guide tamoxifen therapy for breast cancer patients. Tamoxifen 180-189 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 153-159 29473149-2 2018 CYP2D6 metabolizes tamoxifen to its more active metabolite, endoxifen, and patients with reduced CYP2D6 activity have reduced circulating endoxifen concentrations. Tamoxifen 19-28 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 29473149-2 2018 CYP2D6 metabolizes tamoxifen to its more active metabolite, endoxifen, and patients with reduced CYP2D6 activity have reduced circulating endoxifen concentrations. Tamoxifen 19-28 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 97-103 34957551-0 2022 Comparison of adverse drug reactions between tamoxifen and toremifene in breast cancer patients with different CYP2D6 genotypes: a propensity-score matched cohort study. Tamoxifen 45-54 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 111-117 19597703-1 2009 Retrospective studies suggest that single nucleotide polymorphisms in the cytochrome P450 2D6 (CYP2D6) gene predict reduced tamoxifen metabolism, better tolerance and worse treatment outcome. Tamoxifen 124-133 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 74-93 19597703-1 2009 Retrospective studies suggest that single nucleotide polymorphisms in the cytochrome P450 2D6 (CYP2D6) gene predict reduced tamoxifen metabolism, better tolerance and worse treatment outcome. Tamoxifen 124-133 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 95-101 19597703-4 2009 Here, we report a detailed assessment of tamoxifen activity in 19 CYP2D6 HM women, while they were using tamoxifen either for metastatic (n = 5) or for early disease (n = 14). Tamoxifen 41-50 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 66-72 19597703-8 2009 The transvaginal ultrasonographic appearance of the endometrium in CYP2D6*4/*4 patients on tamoxifen is similar as seen in the normal population of tamoxifen users. Tamoxifen 91-100 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 67-73 19597703-10 2009 Serum levels of FSH and SHBG in CYP2D6*4 HM tamoxifen users were in the range of what would be expected during tamoxifen treatment in the general population. Tamoxifen 44-53 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 32-38 19597703-10 2009 Serum levels of FSH and SHBG in CYP2D6*4 HM tamoxifen users were in the range of what would be expected during tamoxifen treatment in the general population. Tamoxifen 111-120 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 32-38 19597703-11 2009 Our findings do show CYP2D6*4/*4 carriers to have activity of tamoxifen on breast cancer, endometrium and serum levels of FSH and SHBG. Tamoxifen 62-71 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 21-27 19597703-12 2009 They support clinical trials prospectively testing the effect of CYP2D6 genetic variability in response to tamoxifen before denying this drug to breast cancer patients only based on their CYP2D6*4 status. Tamoxifen 107-116 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 65-71 34957551-10 2022 These findings suggested that CYP2D6 gene polymorphism played a significant role in predicting liver dysfunction, gynecological diseases and lipid metabolism changes among patients taking tamoxifen or toremifene. Tamoxifen 188-197 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 30-36 19597703-0 2009 Prevalent breast cancer patients with a homozygous mutant status for CYP2D6*4: response and biomarkers in tamoxifen users. Tamoxifen 106-115 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 69-75 34957551-1 2022 CYP2D6 gene polymorphism had a profound impact upon the effect of tamoxifen as adjuvant endocrine therapy in breast cancers. Tamoxifen 66-75 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 34957551-2 2022 However, it had never been reported whether the adverse drug reactions vary by CYP2D6 metabolic status for patients treated with tamoxifen or toremifene. Tamoxifen 129-138 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 79-85 34899282-3 2021 This is mainly due to genetic variants in CYP2D6 gene, as well as other genes encoding proteins involved in the TAM pharmacokinetic and/or pharmacodynamic. Tamoxifen 112-115 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 42-48 34570302-0 2021 Impact of systemic adjuvant therapy and CYP2D6 activity on mammographic density in a cohort of tamoxifen-treated breast cancer patients. Tamoxifen 95-104 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 40-46 34480554-2 2021 Endoxifen, a secondary metabolite resulting from CYP2D6-dependent biotransformation of the primary tamoxifen metabolite, N-desmethyltamoxifen (NDT), is a more potent antiestrogen than either NDT or the parent drug, tamoxifen. Tamoxifen 99-108 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 49-55 34480554-2 2021 Endoxifen, a secondary metabolite resulting from CYP2D6-dependent biotransformation of the primary tamoxifen metabolite, N-desmethyltamoxifen (NDT), is a more potent antiestrogen than either NDT or the parent drug, tamoxifen. Tamoxifen 215-224 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 49-55 34290055-5 2021 We used full CYP2D6 gene sequences obtained with long-read amplicon-based sequencing and cytochrome P450 (CYP) 2D6-mediated tamoxifen metabolism data from a prospective study of 561 patients with breast cancer to train a neural network. Tamoxifen 124-133 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 89-114 34284099-0 2021 CYP2D6 Genotype Predicts Tamoxifen Discontinuation and Drug Response: A Secondary Analyses of the KARISMA Trial. Tamoxifen 25-34 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 34284099-2 2021 This study aims to investigate if CYP2D6 metabolizer status is associated with tamoxifen-related endocrine symptoms, tamoxifen discontinuation, and mammographic density change. Tamoxifen 79-88 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 34-40 34284099-2 2021 This study aims to investigate if CYP2D6 metabolizer status is associated with tamoxifen-related endocrine symptoms, tamoxifen discontinuation, and mammographic density change. Tamoxifen 117-126 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 34-40 34284099-8 2021 Ultrarapid CYP2D6 metabolizers were more likely than other groups to report a clinically relevant change in cold sweats, hot flash, mood swings, being irritable, as well as the overall modified FACT-ES score, after taking tamoxifen. Tamoxifen 222-231 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 11-17 34284099-9 2021 The 6-month tamoxifen discontinuation rates among poor, intermediate, normal, and ultrarapid CYP2D6 metabolizers were 25.7%, 23.6%, 28.6%, and 44.4%, respectively. Tamoxifen 12-21 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 93-99 34284099-11 2021 CONCLUSIONS: Poor CYP2D6 metabolizers are likely to experience an impaired response to tamoxifen, measured through mammographic density reduction. Tamoxifen 87-96 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 18-24 34196110-1 2022 PURPOSE: To evaluate the prognosis of estrogen receptor-positive breast cancer patients with CYP2D6*10 mutant genotypes under tamoxifen or toremifen therapy. Tamoxifen 126-135 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 93-99 34196110-15 2022 CONCLUSIONS: Tamoxifen was less effective in patients with CYP2D6*10 C/T and T/T genotypes. Tamoxifen 13-22 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 59-65 34199712-2 2021 Endoxifen is the most-studied active tamoxifen metabolite, and endoxifen concentrations are highly associated with CYP2D6 activity. Tamoxifen 37-46 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 115-121 34199712-9 2021 CYP2D6 was the primary gene associated with the tamoxifen metabolism pathway, especially the conversion of tamoxifen to endoxifen. Tamoxifen 48-57 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 34199712-9 2021 CYP2D6 was the primary gene associated with the tamoxifen metabolism pathway, especially the conversion of tamoxifen to endoxifen. Tamoxifen 107-116 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 35495161-4 2022 As an example, individuals of African descent (14-34%) harbor an exclusive genetic variant in the gene encoding a liver metabolizing enzyme (CYP2D6) which reduces the efficacy of the breast cancer chemotherapeutic Tamoxifen. Tamoxifen 214-223 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 141-147 35300283-9 2022 Knowing potential medication interactions is critical such as with medications that can lead to serotonin syndrome, concomitant use with monoamine oxidase inhibitors and being aware of p450 drug metabolism is essential for patients taking drugs that utilize the CYP2D6 enzyme for metabolism including tamoxifen. Tamoxifen 301-310 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 262-268 35455627-1 2022 Adherence to treatment and use of co-medication, but also molecular factors such as CYP2D6 genotype, affect tamoxifen metabolism, with consequences for early breast cancer prognosis. Tamoxifen 108-117 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 84-90