Tamoxifen side effects: pharmacogenetic and clinical approach in Mexican mestizos

Tamoxifen metabolism is translated into four genetic phenotypes (GP): genetic poor metabolizer (gPM); genetic intermediate metabolizer (gIM); genetic normal metabolizer (gNM); and genetic ultra-rapid metabolizer (gUM). Although CYP2D6 is involved in tamoxifen biotransformation, its association with tamoxifen side effects (TSE) is limited. Therefore, we evaluated CYP2D6 GP and clinical variables as potential predictors of TSE in Mexican Mestizo patients.

This cross-sectional study evaluated CYP2D6 GP, clinical data, and self-reported TSE in 71 women. Potential predictors were tested in uni- and multivariable models.

Hot flashes (57.75%), arthralgia (45.07%), headache (43.66%), and cramps (39.44%) were the most frequent TSE. Three GP were identified: gPM (2.8%); gNM (93.0%); and gUM (4.2%). In the univariate analysis, none of the GP was predictive of TSE. However, the uni- and multivariable models showed contraceptive use and chemotherapy treatment prior to tamoxifen therapy to be predictive. Two alleles were identified for the first time at unusually high frequencies: CYP2D6*34 (13.2%); and *39 (14.7%).

Our findings indicate that CYP2D6 GP were not significantly predictive of TSE, though two clinical descriptors were. The present results are a valuable contribution to pharmacogenetic characterization of Mexican Mestizo populations who, like other Latin-American groups, are poorly represented in the literature.