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

Breast. 2013 Dec;22(6):1178-83. doi: 10.1016/j.breast.2013.08.011. Epub 2013 Sep 20.

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 < 0.001), cytoplasmic expression of Rad51 (HR 1.87; 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 < 0.001).

Conclusions: ER-negativity, cytoplasmic expression of Rad51 and high Ki-67 are associated with increased risk of BM.

Keywords: Brain metastases; Breast cancer; Estrogen receptor; HER2; Ki-67; Rad51.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis*
  • Brain Neoplasms / secondary*
  • Breast Neoplasms / chemistry*
  • Breast Neoplasms / pathology*
  • Cadherins / analysis
  • Carcinoma, Ductal, Breast / chemistry*
  • Carcinoma, Ductal, Breast / secondary
  • Carcinoma, Lobular / chemistry*
  • Carcinoma, Lobular / secondary
  • Claudin-3 / analysis
  • Claudin-4 / analysis
  • Female
  • Humans
  • Immunohistochemistry
  • Keratin-5 / analysis
  • Keratin-6 / analysis
  • Ki-67 Antigen / analysis
  • Middle Aged
  • Rad51 Recombinase / analysis*
  • Receptor, ErbB-2 / analysis
  • Receptor, ErbB-3 / analysis
  • Receptors, CXCR4 / analysis
  • Receptors, Estrogen / analysis
  • Receptors, Progesterone / analysis
  • Risk Factors
  • Tissue Array Analysis
  • Young Adult

Substances

  • Biomarkers, Tumor
  • CXCR4 protein, human
  • Cadherins
  • Claudin-3
  • Claudin-4
  • Keratin-5
  • Keratin-6
  • Ki-67 Antigen
  • Receptors, CXCR4
  • Receptors, Estrogen
  • Receptors, Progesterone
  • ERBB2 protein, human
  • ERBB3 protein, human
  • Receptor, ErbB-2
  • Receptor, ErbB-3
  • Rad51 Recombinase