[CYP2D6 polymorphisms and tamoxifen: therapeutic perspectives in the management of hormonodependent breast cancer patients]

Abstract

Tamoxifen is a prodrug mainly metabolized by the CY2D6 cytochrome. More than 80 variants of the CYP2D6 gene have been identified. They predict four different enzymatic phenotypes: ultra-rapid metabolizers (UM), extensive metabolizers (EM), intermediate metabolizers (IM) and poor metabolizers (PM). Six retrospectives studies suggest a link between some polymorphisms of the CYP2D6 and tamoxifen efficacy and two studies have found no statistically significant data. Today, level of proof remains insufficient to recommend the testing of a patient's genotype before tamoxifen prescription. Designing prospective studies is necessary before considering therapy strategies based on pharmacogenetics data. In pre-menopausal breast cancer PM or IM patients, an increase in dosage of tamoxifen or a treatment with LH-RH analogues with aromatase inhibitors (AI) may be beneficial instead of the actual recommendations of a 5-year tamoxifen therapy. In postmenopausal EM patients, tamoxifen may be as efficient as AI. In post-menopausal PM patients, a switch strategy may be inferior to a 5-year IA strategy, which would therefore be the standard of care.