Observational studyMolecular oncology2021
Low Z-4OHtam concentrations are associated with adverse clinical outcome among early stage premenopausal breast cancer patients treated with adjuvant tamoxifen.
Observational study in Molecular oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 12 citations in OpenAlex.
- Importance of endocrine treatment adherence and persistence in breast cancer survivorship: a systematic review.BMC cancer · 2023Pooled it
- Influence of endoxifen on mammographic density: results from the KARISMA-Tam trial.Journal of the National Cancer Institute · 2025Trial
- Preliminary results using a kit to measure tamoxifen and metabolites concentrations in capillary blood samples from women with breast cancer.Scientific reports · 2022Trial
- Development and validation of an LC-MS/MS method for the comprehensive quantification of tamoxifen and its metabolites in volumetric absorptive microsampling: clinical application in breast cancer patients.Analytical and bioanalytical chemistry · 2026Article
- Tamoxifen pharmacokinetics and pharmacodynamics in older patients with non-metastatic breast cancer.Breast cancer research and treatment · 2023Article
- Article
- Endoxifen, an Estrogen Receptor Targeted Therapy: From Bench to Bedside.Endocrinology · 2021Review
- HNRNPA2B1 regulates tamoxifen- and fulvestrant-sensitivity and hallmarks of endocrine resistance in breast cancer cells.Cancer letters · 2021Article
- Effect of Genetic Variability in 20 Pharmacogenes on Concentrations of Tamoxifen and Its Metabolites.Journal of personalized medicine · 2021Article
- Generating a Precision Endoxifen Prediction Algorithm to Advance Personalized Tamoxifen Treatment in Patients with Breast Cancer.Journal of personalized medicine · 2021Review
Corrections and comments
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Authors and funding
18 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Low steady-state levels of active tamoxifen metabolites have been associated with inferior treatment outcomes. In this retrospective analysis of 406 estrogen receptor-positive breast cancer (BC) patients receiving adjuvant tamoxifen as initial treatment, we have associated our previously reported thresholds for the two active metabolites, Z-endoxifen and Z-4-hydroxy-tamoxifen (Z-4OHtam), with treatment outcomes in an independent cohort of BC patients. Among all patients, metabolite levels did not affect survival. However, in the premenopausal subgroup receiving tamoxifen alone (n = 191) we confirmed an inferior BC -specific survival in patients with the previously described serum concentration threshold of Z-4OHtam ≤ 3.26 nm (HR = 2.37, 95% CI = 1.02-5.48, P = 0.039). The 'dose-response' survival trend in patients categorized to ordinal concentration cut-points of Z-4OHtamoxifen (≤ 3.26, 3.27-8.13, > 8.13 nm) was also replicated (P-trend log-rank = 0.048). Z-endoxifen was not associated with outcome. This is the first study to confirm the association between a published active tamoxifen metabolite threshold and BC outcome in an independent patient cohort. Premenopausal patients receiving 5-year of tamoxifen alone may benefit from therapeutic drug monitoring to ensure tamoxifen effectiveness.
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