Opportunities of the pharmacogenetic approach to personalized tamoxifen breast cancer therapy: preliminary results

Tamoxifen is the selective modulator of estrogen receptors. Nowadays, it is widely used for treatment of premenopausal women with ER(+) breast cancer likewise for postmenopausal women with treatment contraindications to aromatase inhibitors. Tamoxifen is a prodrug which is metabolized by cytochrome P450 (CYP): CYP2D6, CYP3A5, CYP2C9, CYP2C19 to active metabolites. There is high variability in the CYP genes therefore differences in Tamoxifen metabolism. This article presents preliminary results of genetic testing of 120 patients with breast cancer. Patients responded to the survey questionnaire, then samples of buccal epithelium were taken for genetic analysis of CYP2D6*4, CYP3A5*3, CYP2C9*2,3, CYP2C19*2,3, gene mutations by use of real time PCR. In addition, this article presents demographic features in the prevalence of the most significant polymorphisms of the studied genes. We suppose that routine genetic study before tamoxifen administration would help to predict individual intolerance and increase the efficacy of treatment.

breast cancer, tamoxifen, pharmacogenetics, cytochrome, polymorphism

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