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Are BRCA1- and BRCA2-Associated Breast Cancers Different? Prognosis of BRCA1-Associated Breast Cancer

From the Departments of Human Genetics and Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY.

Address reprint requests to Mark Robson, MD, Departments of Human Genetics and Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021; email robsonm@ mskcc.org.

PURPOSE: To review the available literature regarding the outcome of breast cancer arising in the setting of a germline BRCA1 mutation.

METHODS: Reports of relevant studies obtained from a search of MEDLINE and studies referenced in those reports were reviewed. In addition, data from a previously published study of breast conservation therapy among women of Ashkenazi descent were reanalyzed to discern the effect of germline BRCA1 status.

RESULTS: Although BRCA1-associated breast cancers have been associated repeatedly with poor prognostic features, studies that examine the impact of germline BRCA1 status on outcome have not consistently shown an adverse effect of BRCA1 mutations. In part, this may result from methodologic limitations of earlier trials. Recent studies that examine relatively unselected groups of Ashkenazi women have indicated a negative prognostic effect of specific BRCA1 mutations. It remains to be determined, however, whether BRCA1 status is an independent prognostic factor and whether the findings can be generalized to other mutations.

CONCLUSION: BRCA1-associated breast cancers present with histopathologic features that seem to confer an adverse prognosis, at least in certain subgroups. However, it is not clear whether BRCA1 status has an independent effect on outcome. Until further data become available, treatment for BRCA1-associated breast cancer should be determined by the same factors that influence therapy of nonhereditary disease.

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