Major improvement in the efficacy of BRCA1 mutation screening using morphoclinical features of breast cancer

A family history of breast and/or ovarian cancer is the main criterion used in screening BRCA1 gene carriers. However, ascertaining a patient's family history is a difficult task, which significantly restricts the use of this parameter in clinical practice. Alternative individual criteria that can b e used to identity BRCA1 gene carriers would, therefore, be of great value. In this context, it was recently established that BRCA1-associated breast cancers (BRCA1-BCs) show a specific morphoclinical pattern. In multivariate analyses, the two most discriminant morphoclinical parameters available fo r establishing the BRCA1 status, in addition to an early age at onset, are estrogen receptor negativity (ER-) and poor tumor differentiation (TD3), He re we tested the efficacy of these two morphological parameters as BRCA1 mu tation indicators and investigated their economic impact, in a population-b ased survey on a series of women who developed invasive breast cancer by th e age of 35 years, regardless of their Family history. A high rate of 28.6% of BRCA1 mutations was found to have occurred in the group of tumors with both ER- and TD3 versus only 3.6% in tumors with other profiles (P = 0.007; odds ratio, 10.8), When the sole criterion used was early onset by the age of 35 years, the mutation rate was found to be 8.6%, The resulting cost of testing only women with ER- and TD3 tumors worked out at 30% that of testi ng the whole population of women with cancer by the age of 35 years, and th e sensitivity was found to be of 66%, Lastly, the family history of ER- and TD3 cases with a BRCA1 mutation was investigated retrospectively, and none of these Eases was found to have a particularly extensive family history o f breast and/or ovarian cancer. The use of these morphological features of BRCA1-BCs that are currently typed in clinical practice, therefore, provide s a helpful and cost-effective tool for those making decisions about geneti c screening. This strategy makes it possible to identify gene carriers who would be overlooked using current criteria.