Observational studyThe pharmacogenomics journal2015
Tamoxifen metabolism predicts drug concentrations and outcome in premenopausal patients with early breast cancer.
Observational study in The pharmacogenomics journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 86 papers, 5 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Genetic Study of CYP2D6 Enzyme and Therapeutic Drug Monitoring of Tamoxifen in Premenopausal Women With Breast Cancer
Assessing Effectiveness and Implementation of an EHR Tool to Assess Heart Health Among Survivors (AH-HA)
Who cites it
86 citing papers in PubMed, 5 syntheses or guidelines pooled it, 198 citations in OpenAlex.
- 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
- Impact of CYP2D6 polymorphisms on endoxifen concentrations and breast cancer outcomes.The pharmacogenomics journal · 2018Pooled it
- 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
- Polymorphism at 19q13.41 Predicts Breast Cancer Survival Specifically after Endocrine Therapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2015Pooled it
- Factors affecting inter-individual variability in endoxifen concentrations in patients with breast cancer: results from the prospective TOTAM trial.Breast cancer research and treatment · 2022Trial
- Trial
- In vivo assessment of the metabolic activity of CYP2D6 diplotypes and alleles.British journal of clinical pharmacology · 2015Trial
- Resolving CYP2D6 Structural Complexity with Long-Read Sequencing: Implications for Tamoxifen Precision Dosing in Thai Breast Cancer Patients.Clinical pharmacology and therapeutics · 2026Article
- A multi-ancestry genome-wide study of tamoxifen metabolism and breast cancer recurrence.NPJ breast cancer · 2026Article
- The evolving landscape of pharmacogenomics: Current achievements and future directions.Pharmacological reviews · 2026Review
- Article
- Advances in intratumoral immunotherapy from a neuro-immune-endocrine perspective for breast cancer treatment.Frontiers in oncology · 2026Review
- From Genotype to Therapeutic Monitoring: Enhancing Tamoxifen Efficacy in Breast Cancer Treatment.Journal of clinical pharmacology · 2025Article
- Impact of Complex Genetic and Drug-Drug Interactions on Tamoxifen Metabolism and Efficacy.Journal of personalized medicine · 2025Review
- Comparison of Current Immunotherapy Approaches and Novel Anti-Cancer Vaccine Modalities for Clinical Application.International journal of molecular sciences · 2025Review
- CYP2D6 genotype and outcome in tamoxifen treated early breast cancer.Acta oncologica (Stockholm, Sweden) · 2025Article
- The impact of coadministration of venlafaxine, citalopram or gabapentin on the metabolic activation of tamoxifen.Breast cancer research and treatment · 2025Article
- CYP2D6 polymorphisms and endoxifen concentration in Chinese patients with breast cancer.BMC cancer · 2025Article
- Article
26 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors at 6 institutions in 4 countries.
Funding
Abstract
Tamoxifen is the standard-of-care treatment for estrogen receptor-positive premenopausal breast cancer. We examined tamoxifen metabolism via blood metabolite concentrations and germline variations of CYP3A5, CYP2C9, CYP2C19 and CYP2D6 in 587 premenopausal patients (Asians, Middle Eastern Arabs, Caucasian-UK; median age 39 years) and clinical outcome in 306 patients. N-desmethyltamoxifen (DM-Tam)/(Z)-endoxifen and CYP2D6 phenotype significantly correlated across ethnicities (R(2): 53%, P<10(-77)). CYP2C19 and CYP2C9 correlated with norendoxifen and (Z)-4-hydroxytamoxifen concentrations, respectively (P<0.001). DM-Tam was influenced by body mass index (P<0.001). Improved distant relapse-free survival (DRFS) was associated with decreasing DM-Tam/(Z)-endoxifen (P=0.036) and increasing CYP2D6 activity score (hazard ratio (HR)=0.62; 95% confidence interval (CI), 0.43-0.91; P=0.013). Low (<14 nM) compared with high (>35 nM) endoxifen concentrations were associated with shorter DRFS (univariate P=0.03; multivariate HR=1.94; 95% CI, 1.04-4.14; P=0.064). Our data indicate that endoxifen formation in premenopausal women depends on CYP2D6 irrespective of ethnicity. Low endoxifen concentration/formation and decreased CYP2D6 activity predict shorter DRFS.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.