PREVALENCE OF CYP2D6∗4 AND ITS POSSIBLE RELATION TO THERAPEUTIC OUTCOMES OF ADJUVANT TAMOXIFEN THERAPY IN EGYPTIAN PREMENOPAUSAL WOMEN WITH BREAST CANCER

Abstract

Background: Although tamoxifen is a main adjuvant therapy in estrogen positive breast cancer especially in premenopausal women, reliance on genetic polymorphisms of its CYP2D6 metabolizing enzyme and/or therapeutic drug monitoring of its active metabolite, endoxifen to determine tamoxifen-therapeutic outcomes is debatable. Objective: The goal of the study was to investigate the prevalence of CYP2D6∗4 and possible association between its nonfunctional allele (A) and both tamoxifen-induced adverse effects and cancer relapse in premenopausal breast cancer patients. Method:Polymerase chain reaction -restriction fragment length polymorphism (PCR-RFLP) analysis was applied for detection of CYP2D6∗4 (1846 G>A) genotypes. Results:Genotyping analysis of CYP2D6∗4 showed a minimal allele frequency of 23%. Increased endometrial thickness in mm was significantly correlated with CYP2D6∗4 GA and AA genotypes in comparison with GG genotypes (P< 0.01). No other relations were found between CYP2D6∗4 alleles and other tamoxifen adverse effects (P > 0.9) or cancer relapse (P= 0.7). Conclusion: The prevalence of CYP2D6∗4 polymorphism in Egyptian premenopausal females with breast cancer who are given tamoxifen is similar to that in Caucasians. The nonfunctional allele (A-allele) of CYP2D6∗4 showed a significant association with increased endometrial thickness possibly related to tamoxifen, but no association with other drug adverse effects or cancer relapse.