ReviewThe Lancet. Oncology2009
Genotype-guided tamoxifen therapy: time to pause for reflection?
Review in The Lancet. Oncology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
52 citing papers in PubMed, 5 syntheses or guidelines pooled it, 113 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
- Improving the transparency of meta-analyses with interactive web applications.BMJ evidence-based medicine · 2021Pooled 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
- Metabolism and transport of tamoxifen in relation to its effectiveness: new perspectives on an ongoing controversy.Future oncology (London, England) · 2014Pooled it
- Association between paraoxonase gene and stroke in the Han Chinese population.BMC medical genetics · 2013Pooled it
- Proteogenomic characterization of invasive breast tumors in young women.NPJ breast cancer · 2025Article
- Endoxifen Concentration Is Associated with Recurrence-Free Survival in Hormone-Sensitive Breast Cancer Patients.Cancer research and treatment · 2025Article
- Bayesian Pathway Analysis for Complex Interactions.American journal of epidemiology · 2020Article
- CircRNAs in anticancer drug resistance: recent advances and future potential.Molecular cancer · 2020Review
- Metabolic Pathway Analysis and Effectiveness of Tamoxifen in Danish Breast Cancer Patients.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2020Article
- Integrated Data Analysis of Six Clinical Studies Points Toward Model-Informed Precision Dosing of Tamoxifen.Frontiers in pharmacology · 2020Article
- Time resolved gene expression analysis during tamoxifen adaption of MCF-7 cells identifies long non-coding RNAs with prognostic impact.RNA biology · 2019Article
- CYP2D6-inhibiting medication use and inherited CYP2D6 variation in relation to adverse breast cancer outcomes after tamoxifen therapy.Cancer causes & control : CCC · 2019Article
- Cohort Profile: the Predictors of Breast Cancer Recurrence (ProBe CaRE) Premenopausal Breast Cancer Cohort Study in Denmark.BMJ open · 2018Article
- Concurrent new drug prescriptions and prognosis of early breast cancer: studies using the Danish Breast Cancer Group clinical database.Acta oncologica (Stockholm, Sweden) · 2018Article
- Serum concentrations of active tamoxifen metabolites predict long-term survival in adjuvantly treated breast cancer patients.Breast cancer research : BCR · 2017Article
- CYP2D6 genotype is not associated with survival in breast cancer patients treated with tamoxifen: results from a population-based study.Breast cancer research and treatment · 2017Article
- CYP2C19*2 and CYP2C19*17 variants and effect of tamoxifen on breast cancer recurrence: Analysis of the International Tamoxifen Pharmacogenomics Consortium dataset.Scientific reports · 2017Article
- Cytochrome P450 Allele CYP3A7*1C Associates with Adverse Outcomes in Chronic Lymphocytic Leukemia, Breast, and Lung Cancer.Cancer research · 2016Article
- The Role of MicroRNAs as Predictors of Response to Tamoxifen Treatment in Breast Cancer Patients.International journal of molecular sciences · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 3 countries.
Funding
Abstract
Tamoxifen remains a cornerstone of adjuvant therapy for patients with early stage breast cancer and oestrogen-receptor-positive tumours. Accurate markers of tamoxifen resistance would allow prediction of tamoxifen response and personalisation of combined therapies. 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. In some studies, women with these alleles have a higher risk of recurrence than women with two functional alleles. 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. Ten epidemiology studies on the association between CYP2D6 genotype and breast cancer recurrence report widely heterogeneous results with relative-risk estimates outside the range of reasonable bounds. None of the explanations proposed for the heterogeneity of these results adequately account for the variability and no design feature sets apart any study or subset of studies as most likely to be accurate. The studies reporting a positive association might receive the most attention, because they report a result consistent with the profile of metabolite concentrations; not because they are more reliable by design. We argue that a recommendation for CYP2D6 genotyping of candidates for tamoxifen therapy, and its implicit conclusion regarding the association between genotype and recurrence risk, is premature.
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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.