Background: The prevalence of families eligible for BRCA1/2 mutation testing in the population burden of breast cancer was analysed and the aggregation of breast cancer in these families was explored.
Patients and methods: The families of the Swedish Family-Cancer Database with at least three generations (N=944 723) were classified according to the criteria proposed by the German Consortium for Hereditary Breast and Ovarian Cancer for BRCA1/2 mutation testing. We calculated the proportion of women with breast cancer in the classified families and used standardised incidence ratios (SIRs) to estimate the risk of histology specific breast cancers in families with suspected BRCA1/2 mutations.
Results: Families with two breast cancers before the age of 50 years included 1.8% of the breast cancer patients; 1% of the women with breast cancer belonged to families with breast and ovarian cancers. The SIR of female breast cancer was lowest in families with male breast cancer and highest in families with two women affected by breast cancer under the age of 50 years. The SIRs of medullary breast cancer agreed with the BRCA1 mutation prevalences detected by the German Consortium for Hereditary Breast and Ovarian Cancer.
Conclusions: Most of the breast malignancies in families with male breast cancer are likely to be related to BRCA2 mutations. Non-BRCA1/2 related effects are probably involved in the strong clustering of breast cancer in families with early onset breast and ovarian cancers.