Summary

Abstract

There has been considerable progress in identifying the genetic changes which contribute to familial breast cancer risk, but additional information is needed before individual risk can be reliably ascertained. Women with BRCA 1 germ line mutations probably comprise about half of all patients,vith inherited breast cancer, while mutations to BRCA 2 probably contribute 70% of the remaining patients. Linkage studies in large familial breast cancer pedigrees have indicated that women with BRCA 1 mutation have an 85% life time risk of developing breast cancer, and that approximately half of these women will be diagnosed before age 50. BRCA 1 is a large gene, and the protein consists of more than 1800 amino acids. The initial reports describe seven different mutations, one of which results in complete loss of BRCA 1 m RNA. Many additional mutations are likely to be described, and correlation of genetic studies with outcomes in different familial breast cancer pedigrees are needed before our understanding of the issue of pene-trance and the importance of modifying factors will be sufficient to assist counselling of family members.