Population-Based Study of Changing Breast Cancer Risk in Icelandic BRCA2 Mutation Carriers, 1920 – 2000

Background: Mutations in the BRCA genes increase the risk of breast cancer. Valid estimates of the magnitude of the life-time risk of breast cancer in BRCA gene mutation carriers are needed for genetic counseling. Recent results suggest that penetrance has increased in recent birth cohorts. We exam-ined the cumulative breast cancer incidence and mortality before age 70 over a diagnosis period of 80 years in Icelandic women who carried the BRCA2 founder mutation 999del5. Methods: Information on all breast cancers diagnosed in Iceland since 1911 was obtained from the Icelandic Cancer Registry. Mutation status was determined by molecular anal-ysis of tissue samples for 847 breast cancer probands who were diagnosed from 1921 through 1985 and selected without knowledge of family history of breast cancer. We estimated the cumulative incidence and mortality from breast cance