Background: Epidemiological studies have repeatedly shown that having a family history is a risk factor for female (and male) breast cancer. Some rare families have many (4 or more) cases of early onset breast cancer (some of which also include women with ovarian cancer) which are most clearly explained by an autosomal dominant gene with high penetrance.
Design: Families with multiple cases of early onset breast (and/or ovarian cancer) have been studied using linkage analysis with the intention of finding the chromosomal region containing such genes.
Results: Two predisposition genes, BRCA1 and BRCA2, have been mapped and cloned. Mutations in these genes confer increased risk of cancer, although the precise level of the increased risk is still unclear. The majority of families with four or more cases of breast cancer diagnosed under the age of 60 years are due to mutations in BRCA1 or BRCA2.
Conclusions: The importance of these two genes to familial breast cancer and to breast cancer incidence overall is becoming clearer; the current information is reviewed. The findings can be immediately translated into clinical practice for these multiple case families. The identification of such families raises a number of other important clinical questions concerning patient management.