Prognostic significance of BRCA1, PARP1, and PARP2 in sporadic breast cancer

e22114 Background: Breast cancer susceptibility gene (BRCA1) is a tumor suppressor gene whose mutation is associated with the development of hereditary breast cancer. In sporadic tumors, loss of BRCA1, resulting from reduced expression or incorrect subcellular localization, has been suggested to be associated with prognosis. Cells with BRCA1 loss of function are deficient in DNA double strand break repair thus activating poly(ADP-ribose) polymerases (PARPs) whose catalytic activity is immediately stimulated by DNA strand-breaks. The aim of this study was to evaluate the prognostic value of BRCA1 and PARPs (PARP1 and 2) in sporadic breast cancer. Methods: We merged two previously published Affymetrix gene expression datasets: GSE 1456 (159 patients, median follow up 7 years) and GSE 2494 (249 patients, median follow up 10 years). Microarray data preprocessing was carried out using Bioconductor software (gcrma procedure). Expression of BRCA1, PARP1 and PARP2 mRNA were evaluated as continuous variables. Kaplan Meier survival curves and Cox regression analysis (stratified by database) were used to assess the prognostic capability of the identified biomarkers. Results: High mRNA expression of BRCA1, PARP1 and PARP2 was correlated with an adverse prognosis. Relapse Free Survival (RFS) Hazard Ratio was 1.6 (95% CI, 1.2 to 2.1) for BRCA1 (p = 0.002), 1.7 (95% CI, 1.2 to 2.4) for PARP1 (p = 0.002) and 1.7 (95% CI, 1.3 to 2.3) for PARP2 (p = 0.001). By multivariate analysis all 3 genes resulted independently correlated with RFS. When interaction with systemic adjuvant therapy (107 patients treated) was tested, BRCA1 mRNA expression was strongly associated with treatment: HR 2.3 (95% CI, 1.4 to 3.7, p 0.001); p for interaction = 0.06. Conclusions: This study shows that BRCA1, PARP1 and PARP2 are all significantly associated with prognosis in sporadic breast cancer. No significant financial relationships to disclose.