J Clin Pharmacol

Genotype-guided monitoring improves tamoxifen efficacy

September 15, 2025

Study details: This prospective study evaluated 63 women with ER-positive breast cancer receiving tamoxifen 20 mg/day for ≥3 months. Researchers assessed CYP2D6 genotype and measured steady-state plasma concentrations of tamoxifen and its metabolites using liquid chromatography–tandem mass spectrometry (LC-MS/MS). Patients were classified as normal (NM), intermediate (IM), or ultrarapid metabolizers (UM) based on CYP2D6 activity scores.

Results: Endoxifen levels were significantly lower in IMs (7.13 ng/mL) than NMs (22.66 ng/mL; p<.001). Subtherapeutic endoxifen (<6 ng/mL) was observed in 23.1% of IMs vs. 4.1% of NMs. No significant differences were found in other tamoxifen metabolites.

Clinical impact: Combining CYP2D6 genotyping with therapeutic drug monitoring (TDM) may optimize tamoxifen dosing, reduce subtherapeutic exposure, and improve treatment outcomes. This approach supports personalized endocrine therapy in breast cancer management.

Source:

Mendes Batista AF, et al. (2025, September 5). J Clin Pharmacol. From Genotype to Therapeutic Monitoring: Enhancing Tamoxifen Efficacy in Breast Cancer Treatment. https://pubmed.ncbi.nlm.nih.gov/40910489/