ArticleJournal of the National Cancer Institute2012
CYP2D6 and UGT2B7 genotype and risk of recurrence in tamoxifen-treated breast cancer patients.
Article in Journal of the National Cancer Institute, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 103 papers, 9 of them syntheses that pooled it.
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Who cites it
103 citing papers in PubMed, 9 syntheses or guidelines pooled it, 257 citations in OpenAlex.
- CYP2D6 Phenotype and Breast Cancer Outcomes: A Bias Analysis and Meta-Analysis.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2025Pooled it
- Association between genetic polymorphisms in cytochrome P450 enzymes and survivals in women with breast cancer receiving adjuvant endocrine therapy: a systematic review and meta-analysis.Expert reviews in molecular medicine · 2022Pooled it
- Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 and Tamoxifen Therapy.Clinical pharmacology and therapeutics · 2018Guideline
- Cytochrome P-450 2D6 (CYP2D6) Genotype and Breast Cancer Recurrence in Tamoxifen-Treated Patients: Evaluating the Importance of Loss of Heterozygosity.American journal of epidemiology · 2017Pooled it
- Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Women With Early-Stage Invasive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2016Guideline
- CYP2D6 genotype and adjuvant tamoxifen: meta-analysis of heterogeneous study populations.Clinical pharmacology and therapeutics · 2014Pooled it
- Metabolism and transport of tamoxifen in relation to its effectiveness: new perspectives on an ongoing controversy.Future oncology (London, England) · 2014Pooled it
- Pharmacogenomics of drug-metabolizing enzymes: a recent update on clinical implications and endogenous effects.The pharmacogenomics journal · 2013Pooled it
- CYP2D6 genotype and tamoxifen response for breast cancer: a systematic review and meta-analysis.PloS one · 2013Pooled it
- Therapeutic Drug Monitoring of Endoxifen for Tamoxifen Precision Dosing: Feasible in Patients with Hormone-Sensitive Breast Cancer.Clinical pharmacokinetics · 2022Trial
- Trial
- Augmentation of Endoxifen Exposure in Tamoxifen-Treated Women Following SSRI Switch.Clinical pharmacokinetics · 2016Trial
- A randomized phase II presurgical trial of weekly low-dose tamoxifen versus raloxifene versus placebo in premenopausal women with estrogen receptor-positive breast cancer.Breast cancer research : BCR · 2013Trial
- CYP2D6 metabolism and patient outcome in the Austrian Breast and Colorectal Cancer Study Group trial (ABCSG) 8.Clinical cancer research : an official journal of the American Association for Cancer Research · 2013Trial
- Trial
- Relationships between CYP2D6 phenotype, breast cancer and hot flushes in women at high risk of breast cancer receiving prophylactic tamoxifen: results from the IBIS-I trial.British journal of cancer · 2012Trial
- CYP2D6 genotype and tamoxifen response in postmenopausal women with endocrine-responsive breast cancer: the breast international group 1-98 trial.Journal of the National Cancer Institute · 2012Trial
- CYP2D6 genotype and outcome in tamoxifen treated early breast cancer.Acta oncologica (Stockholm, Sweden) · 2025Article
- Genetic variants in tamoxifen metabolism and early treatment discontinuation among premenopausal breast cancer patients.Breast cancer research and treatment · 2025Article
- CYP2D6 polymorphisms and endoxifen concentration in Chinese patients with breast cancer.BMC cancer · 2025Article
43 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 2 countries.
Funding
Abstract
backgroundAdjuvant tamoxifen therapy substantially decreases the risk of recurrence and mortality in women with hormone (estrogen and/or progesterone) receptor-positive breast cancer. Previous studies have suggested that metabolic conversion of tamoxifen to endoxifen by cytochrome P450 2D6 (CYP2D6) is required for patient benefit from tamoxifen therapy.
methodsTumor specimens from a subset of postmenopausal patients with hormone receptor-positive early-stage (stages I, II, and IIIA) breast cancer, who were enrolled in the randomized double-blind Arimidex, Tamoxifen, Alone or in Combination (ATAC) clinical trial, were genotyped for variants in CYP2D6 (N = 1203 patients: anastrozole [trade name: Arimidex] group, n = 615 patients; tamoxifen group, n = 588 patients) and UDP-glucuronosyltransferase-2B7 (UGT2B7), whose gene product inactivates endoxifen (N = 1209 patients; anastrozole group, n = 606 patients; tamoxifen group, n = 603 patients). Genotyping was performed using polymerase chain reaction-based TaqMan assays. Based on the genotypes for CYP2D6, patients were classified as poor metabolizer (PM), intermediate metabolizer (IM), or extensive metabolizer (EM) phenotypes. We evaluated the association of CYP2D6 and UGT2B7 genotype with distant recurrence (primary endpoint) and any recurrence (secondary endpoint) by estimating the hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) using Cox proportional hazards models. All statistical tests were two-sided.
resultsAfter a median follow-up of 10 years, no statistically significant associations were observed between CYP2D6 genotype and recurrence in tamoxifen-treated patients (PM vs EM: HR for distant recurrence = 1.25, 95% CI = 0.55 to 3.15, P = .64; HR for any recurrence = 0.99, 95% CI = 0.48 to 2.08, P = .99). A near-null association was observed between UGT2B7 genotype and recurrence in tamoxifen-treated patients. No associations were observed between CYP2D6 and UGT2B7 genotypes and recurrence in anastrozole-treated patients.
conclusionThe results do not support the hypothesis that CYP2D6 genotype predicts clinical benefit of adjuvant tamoxifen treatment among postmenopausal breast cancer patients.
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