ArticleBreast cancer research and treatment2015
CYP2D6 genotype- and endoxifen-guided tamoxifen dose escalation increases endoxifen serum concentrations without increasing side effects.
Article in Breast cancer research and treatment, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 2 of them syntheses that pooled it.
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Who cites it
30 citing papers in PubMed, 2 syntheses or guidelines pooled it, 58 citations in OpenAlex.
- Research hotspots and trends in therapeutic drug monitoring of anticancer drugs: a 1990-2024 bibliometric analysis.Frontiers in oncology · 2026Pooled it
- Clinical Pharmacogenetic Testing and Application: Laboratory Medicine Clinical Practice Guidelines.Annals of laboratory medicine · 2017Guideline
- CYP2D6 activity in patients with metastatic breast cancer treated with single agent tamoxifen: results from ECOG-ACRIN E3108.Breast cancer research and treatment · 2025Trial
- Therapeutic Drug Monitoring of Endoxifen for Tamoxifen Precision Dosing: Feasible in Patients with Hormone-Sensitive Breast Cancer.Clinical pharmacokinetics · 2022Trial
- Therapeutic Drug Monitoring-Guided Adjuvant Tamoxifen Dosing in Patients with Early Breast Cancer: A Cost-Effectiveness Analysis from the Prospective TOTAM Trial.Clinical drug investigation · 2022Trial
- Article
- Influence of CYP2D6 polymorphisms on tamoxifen side effects in patients with breast cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Article
- Tamoxifen pharmacokinetics and pharmacodynamics in older patients with non-metastatic breast cancer.Breast cancer research and treatment · 2023Article
- Pharmacokinetics of Tamoxifen and Its Major Metabolites and the Effect of the African Ancestry Specific CYP2D6*17 Variant on the Formation of the Active Metabolite, Endoxifen.Journal of personalized medicine · 2023Article
- Development and Characterization of Novel Endoxifen-Resistant Breast Cancer Cell Lines Highlight Numerous Differences from Tamoxifen-Resistant Models.Molecular cancer research : MCR · 2021Article
- Therapeutic drug monitoring of oral targeted antineoplastic drugs.European journal of clinical pharmacology · 2021Review
- Impairment of endoxifen formation in tamoxifen-treated premenopausal breast cancer patients carrying reduced-function CYP2D6 alleles.British journal of clinical pharmacology · 2021Article
- ClinicalCancers · 2021Review
- Simulation-Based Assessment of the Impact of Non-Adherence on Endoxifen Target Attainment in Different Tamoxifen Dosing Strategies.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Predicting steady-state endoxifen plasma concentrations in breast cancer patients by CYP2D6 genotyping or phenotyping. Which approach is more reliable?Pharmacology research & perspectives · 2020Article
- Exposure-response analysis of endoxifen serum concentrations in early-breast cancer.Cancer chemotherapy and pharmacology · 2020Article
- Repurposing of Diagnostic Whole Exome Sequencing Data of 1,583 Individuals for Clinical Pharmacogenetics.Clinical pharmacology and therapeutics · 2020Article
- Integrated Data Analysis of Six Clinical Studies Points Toward Model-Informed Precision Dosing of Tamoxifen.Frontiers in pharmacology · 2020Article
- Non-Journal of clinical medicine · 2019Article
- Dynamic Effects of CYP2D6 Genetic Variants in a Set of Poor Metaboliser Patients with Infiltrating Ductal Cancer Under Treatment with Tamoxifen.Scientific reports · 2019Article
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Breast cancer patients with absent or reduced CYP2D6 activity and consequently low endoxifen levels may benefit less from tamoxifen treatment. CYP2D6 poor and intermediate metabolizers may need a personalized increased tamoxifen dose to achieve effective endoxifen serum concentrations, without increasing toxicity. 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. The escalated dose was calculated by multiplying the individual's endoxifen level at baseline relative to the average endoxifen concentration observed in CYP2D6 extensive metabolizers by 20 mg (120 mg maximum). 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. In intermediate metabolizers, dose escalation increased endoxifen to levels comparable with those observed in extensive metabolizers. In poor metabolizers, the mean endoxifen level increased from 24 to 81 % of the mean concentration in extensive metabolizers. In all patients, the endoxifen threshold of 5.97 ng/ml (=16.0 nM) reported by Madlensky et al. was reached following dose escalation. CYP2D6 genotype- and endoxifen-guided tamoxifen dose escalation increased endoxifen concentrations without increasing short-term side effects. Whether such tamoxifen dose escalation is effective and safe in view of long-term toxic effects is uncertain and needs to be explored.
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