Polymorphisms in PARP1 predict disease-free survival of triple-negative breast cancer patients treated with anthracycline/taxane based adjuvant chemotherapy

Abstract

Triple-negative breast cancer (TNBC) is a highly aggressive disease and of poor prognosis. It is very important to identify novel biomarkers to predict therapeutic response and outcome of TNBC. We investigated the association between polymorphisms in PARP1 gene and clinicopathological characteristics or survival of 272 patients with stage I-III primary TNBC treated with anthracycline/taxane based adjuvant chemotherapy. We found that after adjusted by age, grade, tumor size, lymph node status and vascular invasion, rs7531668 TA genotype carriers had significantly better DFS rate than TT genotype carriers, the 5 y DFS was 79.3% and 69.2% (P = 0.046, HR 0.526 95% CI 0.280–0.990). In lymph node negative subgroup, DFS of rs6664761 CC genotype carriers was much better than TT genotype carriers (P = 0.016, HR 0.261 95% CI 0.088–0.778) and DFS of rs7531668 AA genotype carriers was shorter than TT genotype carriers (P = 0.015, HR 3.361 95% CI 1.259–8.969). In subgroup of age ≤ 50, rs6664761 TC genotype predicted favorable DFS than TT genotype (P = 0.042, HR 0.405 95% CI 0.170–0.967). Polymorphisms in PARP1 gene had no influence on treatment toxicities. After multivariate analysis, tumor size (P = 0.037, HR = 2.829, 95% CI: 1.063–7.525) and lymph node status (P < 0.001, HR = 9.943, 95% CI: 2.974–33.243) were demonstrated to be independent prognostic factors. Our results suggested that polymorphisms in PARP1 gene might predict the DFS of TNBC patients treated with anthracycline/taxane based adjuvant chemotherapy.