CYP2D6 genotype, antidepressant use, and tamoxifen metabolism during adjuvant breast cancer treatment

Abstract

Background: The efficacy of tamoxifen therapy for the treatment of breast cancer varies widely among individu-als. Plasma concentrations of the active tamoxifen metab-olite endoxifen are associated with the cytochrome P450 (CYP) 2D6 genotype. We examined the effects of concom-itant use of selective serotonin reuptake inhibitor antide-pressants, which are CYP2D6 enzyme inhibitors com-monly prescribed to treat hot flashes in women who take tamoxifen, and genotypes for genes that encode tamox-ifen-metabolizing enzymes on plasma concentrations of tamoxifen and its metabolites. Methods: Eighty patients with newly diagnosed with breast cancer who were begin-ning tamoxifen therapy (20 mg/day orally), 24 of whom were taking CYP2D6 inhibitors, were genotyped for com-mon alleles of the CYP2D6, CYP2C9, CYP3A5, and sulfotrans