Hereditary breast and ovarian cancer: epidemiology, genetics, screening and predictive testing

Inherited predisposition to cancer has become an increasingly important part of the practice of clinical genetics. Hereditary breast and ovarian cancer form a significant part of this new field. There are approximately 13,000 new cases of breast cancer diagnosed every year in Canada, and 5% of these can be expected to have a hereditary basis. Large studies implicated a dominant gene with a population frequency of 0.33% and high penetrance. Linkage analysis localised one such gene to chromosome 17q21 in 1990, and 1994 BRCA1 was cloned. The BRCA1 gene is large, and mutations are spread over the entire gene. There is evidence of common origins for some of the mutations. Early detection of hereditary breast and ovarian cancer is problematic. There is no evidence that early diagnosis by population-based mammography improves survival in sporadic premenopausal breast cancer. Multimodal screening for ovarian cancer has not been adequately assessed. Moreover, there is little evidence that such procedures are more likely to be effective in high-risk groups. Women who may gain initial benefit from the cloning of BRCA1 are from BRCA1-linked families who have living affected relatives. Over the next few years, it is likely that predictive testing for hereditary breast and ovarian cancer will become a routine clinical service in large centres.