Immunohistochemical prediction of brain metastases in patients with advanced breast cancer: The role of Rad51

Abstract Background There are no clinically useful biomarkers predictive of brain metastases (BM) in breast cancer. In this study, we investigated the correlation between expression of selected proteins in the primary tumor and the risk of BM in patients with metastatic breast cancer (MBC). Methods The study included 198 MBC patients (96 with and 102 without BM). Using tissue microarrays derived from the primary tumor, we assessed by immunohistochemical expression of ER, PR, HER2, Ki-67, CK5/6, EGFR, HER3, CXCR4, Rad51, E-cadherin, and claudin 3 and 4. Results Ki-67 ≥14% (hazard ratio [HR] 2.76; P P  = 0.014) and ER-negativity (HR 1.72; P  = 0.029) were associated with increased risk of BM in the multivariate analysis. A three-biomarker profile including ER, Ki-67 and Rad51 vs. other subtypes combined yielded an HR of 4.43 ( P Conclusions ER-negativity, cytoplasmic expression of Rad51 and high Ki-67 are associated with increased risk of BM.