İnvestigation of CYP2D6 gene polymorphisms in patients with breast cancer treated with tamoxifen

Breast cancer is the most common cancer among women and the most common cause of death from cancer in the world. Approximately 75-80% of breast cancers are hormone positive. Tamoxifen is a selective estrogen receptor modulator with high therapeutic efficacy in hormone receptor positive breast cancer patients. Tamoxifen, a prodrug, is converted to its most active metabolite endoxifen by the CYP2D6 enzyme in the liver. Interindividual differences occur in the pharmacological activity of tamoxifen due to polymorphisms in the CYP2D6 gene. Numerous studies have been conducted evaluating the efficacy of CYP2D6 alleles and Tamoxifen therapy. Conflicting results have been obtained in studies. In this study, it was planned to investigate CYP2D6 genotyping and its clinical effect in Tamoxifen treatment. DNA isolation was performed from peripheral venous blood samples of 65 patients participating in the study. Identification of CYP2D6 allelic variants (rs16947, rs35742686, rs3892097, rs5030655, rs5030656, rs1065852, rs28371706, rs28371725) was performed by applying TaqMan® Universal PCR Master Mix and TaqMan® Drug Metabolism Genotyping Assay Mix by Real Time Chain Polymerase (RT-PCR). The metabolizing groups were determined according to the genotype results, and the clinical, pathological characteristics and survival analyzes of the patients were compared between the groups. The mean age of the patients was 40.71±7.68 years, and the mean follow-up period was 84 months±42.06 (6-243 months). As a result of genotyping, 35 (53,8%) patients were determined as Normal Metabolizer and 30 (46,2%) patients as Intermediate Metabolizer. There was no significant difference between the metabolizer groups and the menopausal status, body mass indexes, and histopathological features of the patients. There was no significant difference between the groups in terms of overall survival, recurrence and death. Consistent with previous studies, no significant difference was found between the Normal and Intermediate metabolizer groups in terms of pathological features, recurrence, death, and overall survival. For the individualization and optimization of tamoxifen treatment, prospective studies are needed by increasing the sample and the number of alleles examined.