Breast carcinomas arising in carriers of mutations in BRCA1 or BRCA2: Are they prognostically different?

Purpose: To review the preclinical and clinical stud ies relevant to the pr ognosis and prognostic associations of BRCA1- and BRCA2-associated breast c arcinomas, with an emphasis on research methodology. Methods: Reports of relevant studies obtained from a MEDLINE search, and re ferences from these articles, were critically reviewed. Results: Consistent associations with both favorable (medullary or atypical medullary carcinoma) and unfavorable thigh tumor grade, hormone receptor n egativity, somatic p53 mutation) prognostic characteristics have been found for BRCA1-associated breast carcinomas, Inconsistent results have been dem onstrated for prognostic associations of BRCA2-associated breast tumors, Cl inical studies that have directly assessed the prognosis of these rumors ha ve not shown a clear effect of BRCA1 or BRCA2 mutation, but no study has us ed optimal methodology. In vitro and animal model data suggest a possible i nfluence of these mutations on response to agents that cause double-strand DNA breaks, but clinical data are limited. Conclusion: The elucidation of an identifiable subgroup of breast carcinoma s that result from germline mutations in BRCA1 or BRCA2 may be an important step toward genotype-based understanding of prognosis and choice of therap y in this disease. However, currently there are inadequate data to support use of BRCA1 or BRCA2 status to counsel individuals regarding their prognos is or to select treatment. Well-designed studies of population-based incept ion cohorts of breast cancer patients, which have adequate sample size and complete follow-up, and which use objective outcome criteria and blinding o f outcome assessment, are required to optimally address this question. (C) 1999 by American Society of Clinical Oncology.