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

Hareedy, Mohammad Salem; Taha, Amira F.; Ibrahim, Abeer; Saleh, Medhat A.; Abdelrady, Mohamed A.; EL Desoky, Ehab S.

doi:10.21608/bfsa.2022.271774

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

Document Type : Original Article

Authors

¹ Department of Pharmacology, Faculty of Medicine, Assiut University, Egypt.

² Department of Pharmacology and Toxicology, Faculty of Pharmacy, Assiut University, Egypt.

³ Department of Medical Oncology and Hematological Malignancy, South Egypt Cancer Institute, Assiut University, Egypt.

⁴ Department of Public Health and Community Medicine, Assiut University, Egypt.

⁵ Faculty of Medicine, Assiut University, Egypt.

10.21608/bfsa.2022.271774

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.

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