Germ-line mutations in BRCA1 confer an increased risk of developing breast and ovarian cancer, but little is known about the clinical course of breast cancer in BRCA1 mutation carriers compared with noncarriers. Two recurrent BRCA1 mutations (185delAG and 5382insC) are common ( approximately 1.3%) in Ashkenazi Jews and account for about 20% of breast cancers diagnosed before age 40 in this group. We assayed paraffin-embedded tumor blocks from 117 unselected Ashkenazi Jewish women with primary breast cancer, diagnosed before age 65 at a single institution, for the presence of either of the two BRCA1 mutations. We reviewed the medical records and constructed survival curves for BRCA1-positive and -negative subgroups. Twelve of the women (10.3%) were found to carry BRCA1 mutations (eight mutations were 185delAG, and four were 5382insC). The probability of death from breast cancer in the first 5 years was 35.7% in the BRCA1 mutation-positive group and 4.3% in the 100 women without a mutation (P = 0.0023). The 5-year distant disease-free survival was 68.2% in BRCA1 mutation carriers and 88.7% in noncarriers (P = 0.019). These data suggest that breast cancer occurring in an Ashkenazi Jewish woman carrying a germ-line BRCA1 mutation has an adverse prognosis. This information is available before the diagnosis of breast cancer, and therefore, this finding may have important implications for prevention of breast cancer in BRCA1 mutation carriers.

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