ArticleBreast cancer research and treatment2013
Serum concentrations of tamoxifen and its metabolites increase with age during steady-state treatment.
Article in Breast cancer research and treatment, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 51 citations in OpenAlex.
- Influence of endoxifen on mammographic density: results from the KARISMA-Tam trial.Journal of the National Cancer Institute · 2025Trial
- The Effect of Undaria pinnatifida Fucoidan on the Pharmacokinetics of Letrozole and Tamoxifen in Patients With Breast Cancer.Integrative cancer therapies · 2018Trial
- Evaluation of CYP2D6 enzyme activity using a 13C-dextromethorphan breath test in women receiving adjuvant tamoxifen.Pharmacogenetics and genomics · 2015Trial
- Prolonged Low-Dose Administration of FDA-Approved Drugs for Non-Cancer Conditions: A Review of Potential Targets in Cancer Cells.International journal of molecular sciences · 2025Review
- Effects of tamoxifen on cognitive function in patients with primary breast cancer.British journal of cancer · 2025Article
- Rapamycin inhibits tamoxifen-induced endometrial proliferation in vitro as a pilot approach for endometrial protection in breast cancer.Scientific reports · 2025Article
- Effects of Genetic Polymorphisms of Drug Metabolizing Enzymes and co-Medications on Tamoxifen Metabolism in Black South African Women with Breast Cancer.Clinical pharmacology and therapeutics · 2023Article
- Tamoxifen pharmacokinetics and pharmacodynamics in older patients with non-metastatic breast cancer.Breast cancer research and treatment · 2023Article
- Review
- Titratable Pharmacological Regulation of CAR T Cells Using Zinc Finger-Based Transcription Factors.Cancers · 2021Article
- Article
- Generating a Precision Endoxifen Prediction Algorithm to Advance Personalized Tamoxifen Treatment in Patients with Breast Cancer.Journal of personalized medicine · 2021Review
- Phase 1 study of Z-endoxifen in patients with advanced gynecologic, desmoid, and hormone receptor-positive solid tumors.Oncotarget · 2021Article
- Review
- The Influences of Adherence to Tamoxifen and CYP2D6 Pharmacogenetics on Plasma Concentrations of the Active Metabolite (Z)-Endoxifen in Breast Cancer.Clinical and translational science · 2020Observational
- Serum concentrations of active tamoxifen metabolites predict long-term survival in adjuvantly treated breast cancer patients.Breast cancer research : BCR · 2017Article
- Article
- Tamoxifen Directly Inhibits Platelet Angiogenic Potential and Platelet-Mediated Metastasis.Arteriosclerosis, thrombosis, and vascular biology · 2017Article
- The effect ofOncoTargets and therapy · 2017Article
- Effects ofBreast cancer (Dove Medical Press) · 2017Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
It has been suggested that the concentrations of tamoxifen and its demethylated metabolites increase with age. We measured the serum concentrations of the active tamoxifen metabolites, 4OHtamoxifen (4OHtam), 4-hydroxy-N-desmethyltamoxifen (4OHNDtam, Endoxifen), tamoxifen and its demethylated metabolites. Their relations to age were examined. One hundred fifty-one estrogen receptor and/or progesterone receptor positive breast cancer patients were included. Their median (range) age was 57 (32-85) years. Due to the long half-life of tamoxifen, only patients treated with tamoxifen for at least 80 days were included in the study in order to insure that the patients had reached steady-state drug levels. Tamoxifen and its metabolites were measured by liquid chromatography-tandem mass spectrometry. Their serum concentrations were related to the age of the patients. To circumvent effects of cytochrome (CYP) 2D6 polymorphisms we also examined these correlations exclusively in homozygous extensive metabolizers. The concentrations of 4OHNDtam, tamoxifen, NDtam (N-desmethyltamoxifen), and NDDtam (N-desdimethyltamoxifen) were positively correlated to age (n = 151, p = 0.017, 0.045, 0.011, and 0.001 respectively). When exclusively studying the CYP2D6 homozygous extensive metabolizers (n = 86) the correlation between 4OHNDtam and age increased (p = 0.008). Up to tenfold inter-patient variation in the serum concentrations was observed. The median (inter-patient range) concentration of 4OHNDtam in the age groups 30-49, 50-69, and >69 years were 65 (24-89), 116 (25-141), and 159 (26-185) ng/ml, respectively. We conclude that the serum concentrations of 4OHNDtam (endoxifen), tamoxifen, and its demethylated metabolites increase with age during steady-state tamoxifen treatment. 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. The observed high inter-patient range in serum concentrations of tamoxifen and its metabolites, especially in the highest age group, suggest that use of therapeutic monitoring of tamoxifen and its metabolites is warranted.
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