Women ascertained in this way, and found to carry a mutation in BRCA1 or BRCA2, had very high cancer risks. For BRCA1 mutation carriers, the combined risk of developing either breast or ovarian cancer was 60% (±7%) by age 60 and 83% (±7%) by age 80. For BRCA2 mutation carriers, risk was 33% (±9%) by age 60 and 76% (±13%) by age 80. Furthermore, these risks were significantly higher, at every age, among women born more recently than among women born earlier, a birth cohort effect also seen in prior studies. This trend likely reflects increasing prevalence of nongenetic risk factors for breast cancer, including earlier age of menarche and later ages of childbearing, factors related to improved nutrition and education for women in modern society. Notably, 50% of families found to harbor BRCA1 or BRCA2 mutations had no history of breast or ovarian cancer that would have triggered clinical attention. Female mutation carriers from these low-cancer-incidence families had similar cancer risks to female carriers from families with high cancer incidence. Low-cancer-incidence families were simply smaller, with fewer females who inherited BRCA1 or BRCA2 mutations, and hence fewer females who developed breast or ovarian cancer. Absent population-wide screening, women with BRCA1 or BRCA2 mutations from such families would not have been identified until they developed cancer.