Effect of CYP2C19 genotypes on tamoxifen metabolism and early-breast cancer relapse

CYP2C19*2 and CYP2C19*17 might influence tamoxifen metabolism and clinical outcome. Our aim was to investigate the effect of CYP2C19 genotypes on tamoxifen concentrations and metabolic ratios (MRs) and breast cancer recurrence in a large cohort of Caucasian women . Genetic variants ( CYP2D6 and CYP2C19 genotypes), tamoxifen and metabolites concentrations, baseline characteristics, and breast cancer recurrence from the CYPTAM study (NTR1509) were used. CYP2C19*2 and CYP2C19*17 genotypes were evaluated as alleles and as groups based on CYP2D6 genotypes (high, intermediate and low activity). Log-rank test and Kaplan–Meier analysis were used to evaluate differences in recurrence defined as relapse-free survival (RFS). Classification tree analyses (CTAs) were conducted to assess the levels of interactions per polymorphism ( CYP2D6 and CYP2C19 genotypes) on endoxifen concentrations. No differences in mean concentrations and MRs were observed when comparing CYP2C19 genotypes ( CYP2C19*1/*1 ; CYP2C19*1/*2 ; CYP2C19*2/*2 ; CYP2C19*1/*17 ; CYP2C19*17/*17 ; CYP2C19*2/*17 ). Only significant differences ( p value