The prognostic and predictive significance of PARP-1 in locally advanced breast cancer of Egyptian patients receiving neoadjuvant chemotherapy.

Abstract

PARP-1 is a chromatin-associated enzyme that has a role in DNA repair and cell death. PARP-1 inhibitors are suggested therapy specifically for BRCA deficient breast carcinoma; however, their efficacy in sporadic breast cancer is under investigations. This study aimed to evaluate the PARP-1 in locally advanced breast cancer (LABC) cases to determine its predictive significance for outcome and response to neoadjuvant chemotherapy (NCT). This retrospective study was conducted on 84 LABC cases. Immunohistochemical expression of nuclear PARP-1 (nPARP-1) and cytoplasmic PARP-1 (cPARP-1) was evaluated in pretreatment needle core biopsies (NCBs). Results were correlated with clinicopathologic features, overall survival (OS), disease-free survival (DFS), and response to NCT in postoperative specimens. High nPARP-1expression was observed in 64/84 (76%) of cases and was significantly associated with a lower lymph node stage (P=0.04). High cPARP-1 was observed in 40/84 (48%) of cases and it was significantly associated with lower lymph node stage (P=0.022) and lower tumor grade (P=0.050). High nPARP-1 expression was significantly associated with high cPARP-1 expression (P=0.005). Low cPARP-1 expression was associated with no response to chemotherapy in tumor site (P=0.021). According to the univariate survival analysis, high nPARP-1 and high cPARP-1 were significantly associated to longer OS (P=0.017 and P=0.019, respectively). High nPARP-1 but not cPARP-1 showed trend toward improved OS in multivariate Cox-regression analysis (P=0.053). PARP-1 immunohistochemical expression is a marker of good prognosis and is predictive of response to NCT in LABC.