ArticleBMC pharmacology & toxicology2019
Hormonal status affects plasma exposure of tamoxifen and its main metabolites in tamoxifen-treated breast cancer patients.
Article in BMC pharmacology & toxicology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 23 citations in OpenAlex.
- Factors affecting inter-individual variability in endoxifen concentrations in patients with breast cancer: results from the prospective TOTAM trial.Breast cancer research and treatment · 2022Trial
- Therapeutic Drug Monitoring of Endoxifen for Tamoxifen Precision Dosing: Feasible in Patients with Hormone-Sensitive Breast Cancer.Clinical pharmacokinetics · 2022Trial
- Arctigenin Suppresses Breast Cancer Growth In Vitro and In Vivo Through Subtype-Specific Multi-Targeting Activity.International journal of molecular sciences · 2026Article
- The hidden impact of renal impairment on ribociclib exposure and co-medications: a case report.Cancer chemotherapy and pharmacology · 2026Article
- The effects of tamoxifen and its metabolites on circulating estrogen metabolites among pre- and postmenopausal women.Steroids · 2026Article
- From Genotype to Therapeutic Monitoring: Enhancing Tamoxifen Efficacy in Breast Cancer Treatment.Journal of clinical pharmacology · 2025Article
- Assessing plastic waste associated with LC-MS/MS method validation procedures.Cancer chemotherapy and pharmacology · 2025Article
- Impact of Complex Genetic and Drug-Drug Interactions on Tamoxifen Metabolism and Efficacy.Journal of personalized medicine · 2025Review
- Intestinal P-gp activity is reduced in postmenopausal women under breast cancer therapy.Clinical and translational science · 2024Article
- Analytical and Clinical Validation of Assays for Volumetric Absorptive Microsampling (VAMS) of Drugs in Different Blood Matrices: A Literature Review.Molecules (Basel, Switzerland) · 2023Review
- 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
- Article
- Generating a Precision Endoxifen Prediction Algorithm to Advance Personalized Tamoxifen Treatment in Patients with Breast Cancer.Journal of personalized medicine · 2021Review
- Simplified phenotyping of CYP2D6 for tamoxifen treatment using the N-desmethyl-tamoxifen/ endoxifen ratio.Breast (Edinburgh, Scotland) · 2020Article
- Significance of Targeting VEGFR-2 and Cyclin D1 in Luminal-A Breast Cancer.Molecules (Basel, Switzerland) · 2020Article
- CDK4/6 Inhibitors in Breast Cancer Treatment: Potential Interactions with Drug, Gene, and Pathophysiological Conditions.International journal of molecular sciences · 2020Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTamoxifen is considered a prodrug of its active metabolite endoxifen, which is dependent on the CYP2D6 and CYP3A enzymes. Tamoxifen pharmacokinetic variability influences endoxifen exposure and, consequently, its clinical outcome. This study investigated the impact of hormonal status on the pharmacokinetics of tamoxifen and its metabolites in TAM-treated breast cancer patients.
methodsTAM-treated breast cancer patients (n = 40) previously believed to have CYP3A activity within the normal range based on oral midazolam and phenotyped as CYP2D6 normal metabolizers using oral metoprolol were divided into two groups according to premenopausal (n = 20; aged 35-50 years) or postmenopausal (n = 20; aged 60-79 years) status. All patients were treated with 20 mg/day tamoxifen for at least three months. Serial plasma samples were collected within the 24 h dose interval for analysis of unchanged tamoxifen, endoxifen, 4-hydroxytamoxifen and N-desmethyltamoxifen quantified by LC-MS/MS. CYP activities were assessed using midazolam apparent clearance (CYP3A) and the metoprolol/alfa-hydroxymetoprolol plasma metabolic ratio (CYP2D6). CYP3A4, CYP3A5 and CYP2D6 SNPs and copy number variation were investigated using TaqMan assays.
resultsPostmenopausal status increased steady-state plasma concentrations (Css) of tamoxifen (116.95 vs 201.23 ng/mL), endoxifen (8.01 vs 18.87 ng/mL), N-desmethyltamoxifen (485.16 vs 843.88 ng/mL) and 4-hydroxytamoxifen (2.67 vs 4.11 ng/mL). The final regression models included hormonal status as the only predictor for Css of tamoxifen [β-coef ± SE, p-value (75.03 ± 17.71, p = 0.0001)] and 4-hydroxytamoxifen (1.7822 ± 0.4385, p = 0.0002), while endoxifen Css included hormonal status (8.578 ± 3.402, p = 0.02) and race (11.945 ± 2.836, p = 0.007). For N-desmethyltamoxifen Css, the final model was correlated with hormonal status (286.259 ± 76.766, p = 0.0007) and weight (- 8.585 ± 3.060, p = 0.008).
conclusionThe premenopausal status was associated with decreased endoxifen plasma concentrations by 135% compared to postmenopausal status. Thus, the endoxifen plasma concentrations should be monitored mainly in the premenopausal period to maintain plasma levels above the efficacy threshold value.
trial registrationRBR-7tqc7k.
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