Hareedy, M., Taha, A., Ibrahim, A., Saleh, M., Abdelrady, M., EL Desoky, E. (2022). PREVALENCE OF CYP2D6*4 AND ITS POSSIBLE RELATION TO THERAPEUTIC OUTCOMES OF ADJUVANT TAMOXIFEN THERAPY IN EGYPTIAN PREMENOPAUSAL WOMEN WITH BREAST CANCER. test, 45(2), 935-951. doi: 10.21608/bfsa.2022.271774
Mohammad Salem Hareedy; Amira F. Taha; Abeer Ibrahim; Medhat A. Saleh; Mohamed A. Abdelrady; Ehab S. EL Desoky. "PREVALENCE OF CYP2D6*4 AND ITS POSSIBLE RELATION TO THERAPEUTIC OUTCOMES OF ADJUVANT TAMOXIFEN THERAPY IN EGYPTIAN PREMENOPAUSAL WOMEN WITH BREAST CANCER". test, 45, 2, 2022, 935-951. doi: 10.21608/bfsa.2022.271774
Hareedy, M., Taha, A., Ibrahim, A., Saleh, M., Abdelrady, M., EL Desoky, E. (2022). 'PREVALENCE OF CYP2D6*4 AND ITS POSSIBLE RELATION TO THERAPEUTIC OUTCOMES OF ADJUVANT TAMOXIFEN THERAPY IN EGYPTIAN PREMENOPAUSAL WOMEN WITH BREAST CANCER', test, 45(2), pp. 935-951. doi: 10.21608/bfsa.2022.271774
Hareedy, M., Taha, A., Ibrahim, A., Saleh, M., Abdelrady, M., EL Desoky, E. PREVALENCE OF CYP2D6*4 AND ITS POSSIBLE RELATION TO THERAPEUTIC OUTCOMES OF ADJUVANT TAMOXIFEN THERAPY IN EGYPTIAN PREMENOPAUSAL WOMEN WITH BREAST CANCER. test, 2022; 45(2): 935-951. 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

Bulletin of Pharmaceutical Sciences Assiut University
Volume 45, Issue 2, December 2022, Pages 935-951    PDF (1.1 M)
Document Type: Original Article
DOI: 10.21608/bfsa.2022.271774
Authors
Mohammad Salem Hareedy1; Amira F. Taha* 2; Abeer Ibrahim3; Medhat A. Saleh4; Mohamed A. Abdelrady5; Ehab S. EL Desoky1
1Department of Pharmacology, Faculty of Medicine, Assiut University, Egypt.
2Department of Pharmacology and Toxicology, Faculty of Pharmacy, Assiut University, Egypt.
3Department of Medical Oncology and Hematological Malignancy, South Egypt Cancer Institute, Assiut University, Egypt.
4Department of Public Health and Community Medicine, Assiut University, Egypt.
5Faculty of Medicine, Assiut University, Egypt.
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.
          
Keywords
Tamoxifen; CYP2D6*4; premenopausal Egyptian females; breast cancer
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