Breast cancer susceptibility testing: past, present and future

Breast cancer is a genetic disease. The cancer phenotype is defined by a complex interplay between oncogenes, tumor-suppressor genes and epigenetic factors. Only 5-10% of all breast cancers can be attributed to one of several breast cancer familial syndromes, the most common of which is the hereditary breast and ovarian syndrome caused by deleterious mutations of the BRCA1 or BRCA2 tumor-suppressor genes. The functions of the BRCA proteins are not fully understood, although it is clear that they play a role in the control of transcription, regulation of the cell cycle and management of DNA damage. The inheritance of a deleterious BRCA mutation is accompanied by a 50-80% risk of developing breast cancer, 60% risk of developing a contralateral breast cancer and 15-25% risk of developing ovarian cancer. The clinical management of BRCA heterozygotes involves several strategies of primary, secondary and tertiary prevention. These include risk-reducing surgery, chemoprevention, lifestyle changes and increased surveillance. As we move beyond the 10-year anniversary of the discovery of the BRCA genes, we are inevitably led to thoughtful reflection on the impact of these genes in regards to the greater problem of sporadic breast cancer.