Tissue-based predictors of germ-line BRCA1 mutations: implications for triaging of genetic testing.

BRCA testing of patients with breast cancer considered at high risk for having a germ-line BRCA mutation usually consists of comprehensive mutational analysis of both BRCA1 and BRCA2. A more cost-effective strategy of triaging patients for analysis of a single gene could be adopted if tissue-based predictors indicated a high risk specifically for either BRCA1 or BRCA2. To identify potentially useful tissue-based predictors of BRCA mutation status in breast cancer, we evaluated multiple histopathologic features of invasive breast carcinoma on archival tissue sections from 196 high-risk patients who had undergone BRCA testing, and we analyzed which individual or combination of features was most associated with BRCA mutations.