Prognosis of BRCA1 and 2-associated ovarian cancers

About 10% of epithelial ovarian cancers have a hereditary basis. Germline mutations in the BRCA1 and BRCA2 breast/ovarian cancer susceptibility genes are thought to be responsible for most hereditary ovarian cancers. In contrast, about 90% of ovarian cancers arise due to accumulation of somatic mutations. In sporadic ovarian cancers, it has been shown that alterations in the p53 tumor suppressor gene and the HER-2/neu oncogene are associated with advanced stage and poor outcome. Other genetic alterations, such as microsatellite instability have been associated with favorable prognosis in colon and endometrial cancers. In view of this, it is plausible that BRCA1 and 2-associated ovarian cancers might also have a characteristic clinical phenotype. Clinical studies of BRCA1 and 2-associated ovarian cancer have been difficult to perform because no single institution has identified a large number of cases. It appears that the strongest clinical correlate of BRCA1 mutation in ovarian cancer is papillary serous histology. Although most BRCA1-associated ovarian cancers present at an advanced stage, in some studies survival of BRCA1 mutation carriers has been relatively favorable compared to controls. Other studies have not confirmed this association, however. The relative prognosis of ovarian cancers with BRCA2 mutations remains essentially unstudied. Larger collaborative studies are needed to characterize better the clinical features and prognosis of BRCA1 and 2-associated ovarian cancers.