Evaluation Of Neutrophil Gelatinase-Associated Lipocalin (Ngal) As Predictor Of Response To Neoadjuvant Chemotherapy (Nact) In Primary Breast Cancer.

595 Background: In our previous work we showed that NGAL, a protein involved in the regulation of proliferation and differentiation, is overexpressed in human breast cancer (BC) and predicts poor prognosis. In NACT pathological complete response (pCR) is a predictor for outcome. The aim of this study was to evaluate NGAL as a predictor of response to NACT and to validate NGAL as a prognostic factor for clinical outcome in patients with primary BC. Methods: Immunhistochemistry was performed on tissue microarrays from 855 core biopsies from BC patients, who underwent NACT in the GeparTrio trial. NGAL expression was evaluated according to the Allred score. Primary endpoints were pCR, disease-free survival (DFS) and overall survival (OS). For statistical analysis Pearson’s and Fisher’s exact test as well as Kaplan-Meier analysis and Cox proportional hazard models were used. Results: NGAL was detected in 42.2% of the breast carcinomas in the cytoplasm. NGAL expression correlated with negative hormone receptor (HR) status (p = 0.038). NGAL expression and staining intensity were significantly associated with higher pCR rates in patients with positive HR status (p = 0.033). In addition, strong NGAL expression correlated with higher pCR rates in node negative patients (p = 0.038), patients with histological grade 1 or 2 (p = 0.036) tumors and a tumor size < 40 mm (p = 0.031). In univariate survival analysis, positive NGAL expression as well as strong staining intensity correlated with decreased DFS (HR = 1.818; CI = 1.294 – 2.556) in the entire cohort (p = 0.0005) and different subgroups, including HR, estrogen and progesterone receptor positive patients (p = 0.0019; p = 0.0019; p = 0.0027). Similar results were shown for intense staining and decreased OS. In multivariate analysis, NGAL expression remained an independent prognostic factor for DFS (HR = 1.886; CI = 1.249 – 2.848). Conclusions: In low-risk subgroups, NGAL was found to be a predictive marker for pCR after NACT. Furthermore, NGAL could be validated as an independent prognostic factor for decreased DFS in primary human BC.