Determination of the frequency of CYP2D6 polymorphisms in Brazilian women and literature review

Abstract

Introduction: Tamoxifen (TMX), considered a standard endocrine therapy for steroid receptorpositive breast cancer, is metabolically activated to endoxifen, which presents a higher affinity for hormone receptors and is the chief molecule mediating the therapeutics effects of TMX. The biotransformation of TMX to endoxifen occurs through the activity of P450 CYP2D6, and the gene coding this enzyme presents genetic polymorphisms that decrease the activity of this metabolic pathway, and possibly, the clinical effectiveness of TMX. Objective: The aim of this study was to evaluate the frequency of the polymorphisms CYP2D6 *3, *4, *5, *6, and *10, and of the TMX metabolic phenotypes in breast cancer patients followed by the authors at the Oncology Center of the Sírio-Libanês Hospital, as well as to review this subject in the literature. Methods: Peripheral blood samples from 30 patients were sent to a reference laboratory for analysis using polymerase chain reaction-restriction fragment length polymorphisms. Results: There was heterozygosis of CYP2D6*4 and *10 in 33 and 38% of women, respectively. Based on the metabolic phenotype classification previously described 27% of the women were intermediate, and 3% were poor-metabolizers; such patients have almost twice the risk of recurrence of breast cancer during treatment with TMX, as described in some recent series. We have also detected an unexpected high prevalence of heterozigosis of the *10 polymorphism in this population. Conclusions: Prospective studies are ongoing to define the relevance of the CYP2D6 polymorphisms in the choice of hormone adjuvant therapy for hormone-positive breast cancer patients.