Pharmacogenetic prediction of tamoxifen efficiacy and adverse effects in hormonal dependent breast karcinoma patients.

ABSTRACT/SUMMARY Background: The clinical efficacy of tamoxifen therapy may be modified by the drug-metabolizing enzymes and transporting molecules involved into the pharmacokinetics of tamoxifen. The aim of this study was to evaluate the association of CYP2D6, ABCB1 polymorhisms and comedication with efficacy and safety of tamoxifen treatment. Methods: Totally 258 women with hormonal positive breast carcinoma were retrospectively evaluated in relation to CYP2D6, ABCB1 polymorphisms and comedication. Results: CYP2D6 polymorphisms or co-medication affecting CYP2D6 activity demonstrated no statistically significant effect on the efficacy of tamoxifen therapy or adverse event incidence; there was only a trend towards shortening the time to event (TTE) in CYP2D6 poor metabolizers. ABCB1 polymorphism rs2032582 was not associated with clinical outcomes, while a trend towards an increase of TTE in variant allele carriers was noted. The ABCB1 polymorphism rs1045642 demonstrated statistical significance in premenopausal patients (p = 0.0012, HR 0.69 (95% CI 0.21 to 2.31), and its significant association was noted with gynaecological /vasomotor adverse events (p = 0.0221, HR = 1.0588), with no evidence of the influence on the incidence and onset of venous complications. Conclusions: Although this work did not show..