Impact of CYP2D6, CYP2C9/19, CYP3A4, UGT, and SULT Variability on Tamoxifen Metabolism in Breast Cancer Treatment

Abstract

In hormone-receptor-positive breast cancer, the main treatment is tamoxifen. Tamoxifen is a weak antiestrogen that requires prior activation to its most active metabolite, endoxifen, which has superior antiestrogenic activity. In the search for predictive biomarkers to optimize treatment and reduce tamoxifen resistance, studies have concluded that endoxifen concentrations are associated with CYP2D6 activity and that the concentration of endoxifen and other metabolites (whose activities are also linked to the activity of other pharmacogenes) may be associated with tamoxifen efficacy. The aim of this review is to highlight the evidence concerning the contribution of pharmacogenes (CYP2D6, CYP2C9/19, CYP3A4, UGT, and SULT) to tamoxifen metabolism and the effect of the genetic variation to which they are subject on the concentration of active tamoxifen metabolites.