ArticleBreast cancer research and treatment2017
An Antiestrogenic Activity Score for tamoxifen and its metabolites is associated with breast cancer outcome.
Article in Breast cancer research and treatment, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 21 citations in OpenAlex.
- Effect of Genetic Variability in 20 Pharmacogenes on Concentrations of Tamoxifen and Its Metabolites.Journal of personalized medicine · 2021Article
- Article
- Generating a Precision Endoxifen Prediction Algorithm to Advance Personalized Tamoxifen Treatment in Patients with Breast Cancer.Journal of personalized medicine · 2021Review
- Volumetric Absorptive Microsampling as a New Biosampling Tool for Monitoring of Tamoxifen, Endoxifen, 4-OH Tamoxifen and N-Desmethyltamoxifen in Breast Cancer Patients.Drug design, development and therapy · 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
- Nuclear receptor crosstalk - defining the mechanisms for therapeutic innovation.Nature reviews. Endocrinology · 2020Review
- Exposure-response analysis of endoxifen serum concentrations in early-breast cancer.Cancer chemotherapy and pharmacology · 2020Article
- Therapeutic Drug Monitoring of Oral Anti-Hormonal Drugs in Oncology.Clinical pharmacokinetics · 2019Review
- Cost-effectiveness of monitoring endoxifen levels in breast cancer patients adjuvantly treated with tamoxifen.Breast cancer research and treatment · 2018Article
- Serum concentrations of active tamoxifen metabolites predict long-term survival in adjuvantly treated breast cancer patients.Breast cancer research : BCR · 2017Article
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Authors and funding
13 authors at 7 institutions in 2 countries.
Funding
Abstract
purposeEndoxifen concentrations have been associated with breast cancer recurrence in tamoxifen-treated patients. However, tamoxifen itself and other metabolites also show antiestrogenic anti-tumor activity. Therefore, the aim of this study was to develop a comprehensive Antiestrogenic Activity Score (AAS), which accounts for concentration and antiestrogenic activity of tamoxifen and three metabolites. An association between the AAS and recurrence-free survival was investigated and compared to a previously published threshold for endoxifen concentrations of 5.97 ng/mL. PATIENTS AND
methodsThe antiestrogenic activities of tamoxifen, (Z)-endoxifen, (Z)-4-hydroxytamoxifen, and N-desmethyltamoxifen were determined in a cell proliferation assay. The AAS was determined by calculating the sum of each metabolite concentration multiplied by an IC
resultsAn AAS threshold of 1798 was associated with recurrence-free survival, hazard ratio (HR) 0.67 (95% confidence interval (CI) 0.47-0.96), bias corrected after bootstrap HR 0.69 (95% CI 0.48-0.99). The concordance indices for AAS and endoxifen did not significantly differ; however, using the AAS threshold instead of endoxifen led to different dose recommendations for 5.2% of the patients.
conclusionsEndoxifen concentrations can serve as a proxy for the antiestrogenic effect of tamoxifen and metabolites. However, for the aggregate effect of tamoxifen and three metabolites, defined by an integrative algorithm, a trend towards improving treatment is seen and moreover, is significantly associated with breast cancer recurrence.
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