Association between genetic polymorphisms of CYP2D6 and efficacy and side effects of tamoxifen in breast cancer patients

Background and Aims: Breast cancer is the most common cancer in women and 55-75% of breast cancers are hormone receptor-positive cases. Tamoxifen is a prodrug that is used as standard treatment for patients with hormone receptor-positive premenopausal. Efficacy and toxicity of tamoxifen, varies among individuals. Tamoxifen is converted to active metabolites via the CYP2D6 ,which in cytochrome P450 system in the liver. CYP2D6 phenotypes can be determined which can demonstrated drug metabolism according to allele groups.Method: This study including the patients who used tamoxifen and were diagnosed early and locally advanced breast cancer between the years of 2007-2011. Peripheral venous blood samples were taken from patients. The patients were divided into metabolizer groups by identifying CYP2D6 gene polymorphisms with using the method of multiplex PCR. Gene polymorphisms and clinical characteristics of patients were compared. Chi-Square test was used to compare categorical measures between the two groups. Log-Rank test was used with Kaplan-Meier analysis to detect disease-free survival time.Results: Follow-up of patients was 6-71 months (mean=32 months), mean age 44.81 ± 6.44. CYP2D6 gene polymorphisms were allocated as 5.2%, high-speed, 77.1%, normal, 11.5% medium, 2.1% poor metabolizer . A significant relationship wasn?t found between CYP2D6 gene polymorphism and breast cancer?s pathological features. Flushing, vaginal dryness, weight gain, depression, hepatosteatosis, HDL and LDL levels were observed statistically no significant correlation, but increase cholesterol and triglyceride levels were found statistically significant. It was observed that endometrial thickness was statistically significantly increased (p=0.019). It was observed that metastases occur in 5.2% of patient?s at follow-up. Kaplan-Meier method using the log-rank test, the relationship was evaluated between the CYP2D6 gene polymorphism and metastasis and no significant difference (p=0.737) were determined.Conclusion: Between CYP2D6 genetic polymorphism with the various parameters of the disease in patients using tamoxifen, no significant relationship were observed between CYP2D6 genotypes with the pathological features and side effects of cancer. When the effect of the lipid profile was compared, it was found that the patients using tamoxifen and CYP2D6 genotypes except poor metabolizer had elevated cholesterol levels. This rise in cholesterol levels were found that it was more important than the triglyceride levels. Due to the short duration of follow-up and the number of patients with metastasis affects the reliability of the method of analysis. In order to obtain reliable results longer follow-up period are needed.According to this study, polymorphisms of CYP2D6 genotype didn?t affect the result of tamoxifen treatment.