Abstract The prodrug tamoxifen is the standard endocrine treatment for estrogen receptor-positive breast cancer. Its effect depends on activation by the CYP2D6 enzyme, which is encoded by a highly polymorphic gene that varies according to ethnicity. The most important polymorphic variants are *4 (abolished enzyme activity), *10 and *17 (decreased enzyme activity) found in 25%, 38-70% and 35% of Caucasians, Asians and Africans, respectively, resulting in low endoxifen levels (a major metabolite), a lack of response to tamoxifen and a poor prognosis. There is a widespread racial miscegenation in Brazil and the country's public health care system has made tamoxifen available and free of charge to all women with hormone-sensitive breast tumor despite the undetermined genetic profile of these patients.This study aims to evaluate polymorphism frequency of the CYP2D6*4, *10 and *17 alleles in Brazilian breast cancer patients under tamoxifen treatment and metabolism phenotype. Methods: The study was approved by the Internal Review Board of the Federal University of Piauí. All patients signed an informed consent term before study entry. Sixty-five women with estrogen and progesterone receptor-positive and Her-2 negative breast carcinomas were enrolled in the study. A 3-ml peripheral blood sample was collected from each patient, using specific polymerase chain reaction technique (PCR) to analyze haplotypes *1, *4, *10 and *17, determined by studies of different Single-Nucleotide Polymorphism (SNP). Microsoft Office Excel software 2010 was used to compile and analyze the data obtained. Results: The frequency of CYP2D6 alleles *4, *10 and *17 was 17%, 37% and 3%, respectively. Haplotype *1/*10 was present in 26%, while the phenotype of intermediate metabolism occurred in 12% of the women studied. Conclusion: The present study showed a polymorphism frequency of CYP2D6, mainly of allele *10 and a deficiency in tamoxifen metabolism, characterized by intermediate metabolism in 12% of the women studied. Nevertheless, further studies must be developed with a larger sample of women to study not only the presence of the polymorphic variant but also disease prognosis. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-09-15.
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