Increasing Tamoxifen Dose in Breast Cancer Patients Based on CYP2D6 Genotypes and Endoxifen Levels: Effect on Active Metabolite Isomers and the Antiestrogenic Activity Score

Tamoxifen (Tam), the major drug for estrogen receptor (ER)‐positive breast cancer, is converted to its active metabolites, Z‐ and Z′‐endoxifen and 4‐OH‐Tam isomers, primarily by cytochrome P450 CYP2D6. In 117 patients taking 20 mg/day of Tam, we determined CYP2D6 genotypes and measured the plasma levels of Tam metabolites. The Z‐endoxifen levels increased while Z′‐endoxifen levels decreased with increasing metabolizer phenotype activity (MPA) score (P ≤ 0.0004). The dosage in patients with endoxifen