Cytochrome P450 2D6 polymorphisms of Thai patients with breast cancer and their outcomes of adjuvant tamoxifen.

Abstract

e11037 Background: The clinical outcomes of breast cancer patients treated with tamoxifen may be influenced by the activity of cytochrome P450 2D6 (CYP2D6) enzyme because tamoxifen is metabolized by CYP2D6 to its active forms of antiestrogenic metabolite, 4-hydroxytamoxifen and endoxifen. We evaluated Cytochrome P450 2D6 SNPs and the influences of tamoxifen efficacy in adjuvant treatment of breast cancer in Ramathibodi hospital. Methods: Peripheral blood DNA samples from 38 patients who had disease recurrence during adjuvant tamoxifen treatment, and from 38 patients who had completed 5 years of tamoxifen without recurrence of breast cancer were isolated and genotyped for CYP2D6*4 by RFLP method, and CYP2D6*10 by PCR and DNA sequencing method. Disease free survival and correlation with genotypes were analyzed by Kaplan-Meier method, and log-rank test. Results: Of 76 analyzed patients, 42%, 36% and 22% of the patients carried the CYP2D6 *10/*10, wt/*10 and wt/wt genotypes respectively. There was no discernible correlation between clinicopathological parameters and the patterns of CYP2D6 *10 genotype. We found no significant difference in DFS among these three groups of patients (the mean DFS were 42.94 months for *10/*10 patients, not reach for wt/*10 patients and 60 months for wt/wt patients, p=0.128). One patient had both CYP2D6 wt/*4 and *10/*10. We found common SNPs of CYP2D6*10 188C>T with allele frequency 59.87 %. SNP of CYP2D6*4 1934G>T was detected with allele frequency 0.66%. Both SNPs frequencies were concordance to previous reports in Asian population. Conclusions: The polymorphisms of CYP2D6*10 do not influence the clinical outcomes of Thai breast cancer patients receiving adjuvant tamoxifen.