ABSTRACT
Double strand breaks induced by genotoxic agents, if inappropriately repaired, will cause cell death or induce cancer. Poly(ADP-ribose) polymerase-3 (PARP-3) serves a role in double strand break repair, and may be involved in tumorigenesis. To the best of our knowledge, the role of PARP-3 in breast cancer has not yet been examined. In the present study, the expression of PARP-3 was investigated in 493 breast cancer samples and 54 tumor-adjacent control samples using tissue-microarray-based immunohistochemistry. PARP-3 expression was higher in breast cancer samples compared with control samples. PARP-3 overexpression was significantly associated with histological grade II-III (P=0.012). In addition, PARP-3 overexpression was significantly associated with shorter disease-free survival (DFS; P=0.027) time and exhibited a tendency toward shorter overall survival (OS; P=0.183) time in patients with breast cancer compared with patients with lower PARP-3 expression, particularly in BRCA1-positive patients (P=0.004 for disease-free survival and P=0.095 for OS). Multivariate Cox regression analysis indicated that PARP-3 was an independent prognostic factor in patients with breast cancer. Furthermore, it was revealed that PARP-3 overexpression was associated with shorter survival time in patients with cyclophosphamide/doxorubicin or epirubicin/5-fluorouracil (CAF/CEF) chemotherapy compared with low PARP-3 expression, but not in patients with CAF/CEF + docetaxel chemotherapy. The present study suggested that PARP-3 may be used as a biomarker for predicting the clinical outcome of patients receiving chemotherapy, and targeting PARP-3 may be a potential therapeutic strategy for the treatment of breast cancer.