Methods. We studied 80 women in whom breast cancer was diagnosed before the age of 35, and who were not selected on the basis of family history. Genomic DNA was studied for BRCA1 mutations by analysis involving singlestrand conformation polymorphisms and with allele-specific assays, Alterations were defined by DNA sequencing.

Results. Germ-line BRCA1 mutations were identified in 6 of the 80 women, Four additional rare sequence variants of unknown functional importance were also identified, Two of the mutations and three of the rare sequence variants were found among the 39 women who reported no family history of breast or ovarian cancer. None of the mutations and only one of the rare variants was identified in a reference population of 73 unrelated subjects.

Conclusions. Alterations in BRCA1 were identified in approximately 10 percent of this cohort of young women with breast cancer, The risk of harboring a mutation was not limited to women with family histories of breast or ovarian cancer, These results represent a minimal estimate of the frequency of BRCA1 mutations in this population. Comprehensive methods of identifying BRCA1 mutations and understanding their importance will be needed before testing of women in the general population can be undertaken.