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Genetic risk and breast cancer survival: another link in the chain of evidence.

The discovery of the BRCA1 and BRCA2 genes was an important milestone in breast cancer research. Ongoing investigation of cancer genes is sure to improve our knowledge of cancer biology and may speed development of new cancer treatments and prevention strategies. As this research effort goes forward, however, puzzling questions need to be addressed concerning the clinical effects of mutations in the BRCA1 and BRCA2 genes. We do not understand why the degree of cancer risk conferred by mutations is variable or why some mutation carriers develop breast cancer, others develop ovarian cancer, and some develop both. We do not know whether the cancers occurring in mutation carriers are essentially the same or significantly different from those occurring in noncarriers. Breast cancer occurs at an earlier age in mutation carriers, and a higher prevalence of adverse pathobiologic features has been reported in breast cancers occurring in BRCA1 mutation carriers. (1). These observations raise concern that mutationassociated cancers are more aggressive and result in higher mortality rates. A new study (2) reported in this issue of the Journal addresses the question of cancer survival. Lee et al. found no difference in breast or ovarian cancer survival by mutation status. This conclusion was based on a survey of Ashkenazi Jewish