Correlation between in vitro chemotherapy sensitivity and PARP-1 expression in patients with breast cancer

10627 Background: Based on its potential use as a therapeutic target through PARP inhibitors expression of Poly-A-Ribose-Polymerase-1 (PARP-1) has come into scientific focus. Furthermore, it could be demonstrated that cytoplasmic PARP-1 expression varies depending on molecular breast cancer subtypes and that it correlates with an increased response to neoadjuvant taxane-anthrazykline containing chemotherapy (von Minckwitz et al., J Clin Oncol 2011). In-vitro-chemotherapy sensitivity and resistance assays (CSRAs) are a means to directly measure chemotherapy sensitivity in a given tumor uninfluenced by host factors. Methods: We conducted a systematic immunohistochemical tissue-microarray (TMA)-based analysis of 550 samples of invasive breast cancers to evaluate the expression of a set of molecular markers including estrogen receptor (ER), progesterone receptor (PR) and HER2 as well as PARP-1. Triple negative breast cancers (TNBC) were identified through lack of (over-)expression of ER, PR and HER2. All carcinomas were analyzed in an in vitro CSRA protocol for epirubicin/docetaxel (ED) and epirubicin/cyclophosphamide (EC). In-vitro-chemotherapy sensitivity was analyzed using an adenosine triphosphate (ATP) bioluminescence assay. Results: Moderate/high expression of PARP-1 was found in 48 and 33% of cases with TNBC and non-TNBC, respectively (p=0.015). No correlation between TNBC phenotype and cytoplasmic expression was observed. However, increased expression of both cytoplasmic and nuclear PARP-1 was correlated with an increased in-vitro sensitivity against ED (p=0.012 and 0.025, respectively) but not EC (p=0.27 and 0.62, respectively). Conclusions: Our results support previous observations demonstrating a significant correlation between expression of PARP-1 and an increased sensitivity against taxane-anthracycline chemotherapy independent of tumor phenotype.