Impact of CYP2D6 polymorphisms on the efficacy of tamoxifen in Iraqi women with breast cancer

Abstract

Background: Tamoxifen remains the primary therapeutic option for breast cancer treatment and for the primary prevention of metastatic disease. Understanding the variability in tamoxifen response may provide clues to help personalize cancer treatment as well as maximize the therapeutic efficacy. One area of particular interest that merits attention in hormonal therapy is the impact of the CYP2D6 genetic polymorphisms on tamoxifen metabolism and consequently, on patient The aim of the present study was to investigate the impact of the CYP2D6 genetic polymorphism on clinical outcome in Iraqi breast cancer patients who were candidates for tamoxifen therapy. Methods: Comprehensive CYP2D6 genotyping was performed in 140 Iraqi women with breast cancer who were women on adjuvant treatment with tamoxifen. Breast cancer patients recruited into the study were divided into two groups: seventy breast cancer women who had no history of recurrence at the time of sampling and had a long time on tamoxifen without recurrence and seventy breast cancer women who had recurrence at the time of sampling after one year of treatment with tamoxifen therapy. Recurrence free survival (RFS) was determined in the recruited patients.  Results: Multiple genetic variants of the gene encoding the CYP2D6 enzyme were detected with significant differences in their frequencies and percentages in both recurrent and non-recurrent groups of breast cancer patients. The findings of this study suggest that interindividual variation in clinical outcome may be related to genetic variation in CYP2D6 enzyme, which is characterized by variable RFS periods. Conclusions: This study revealed that the CYP2D6 enzyme of breast cancer patients who participated in this study is highly polymorphic. The CYP2D6 gene of study participants exhibited different allelic combinations with variable frequencies. The multiple genetic variants (alleles) of the gene encoding the CYP2D6 enzyme exhibited significant differences in their frequencies and percentages in both recurrent and non-recurrent groups of breast cancer patients. .The study revealed variable Recurrence free survival (RFS) with highly polymorphic gene. Our study quotes the presence of increased CYP2D6 enzyme polymorphism is associated with variable clinical response.