Managing hereditary ovarian cancer risk

Ovarian cancer is the fourth leading cause of cancer deaths in American wom en. About 10% of cases are thought to have a hereditary basis, and family h istory is the strongest known risk factor. In the past, prophylactic oophor ectomy has been advocated for women with two or more affected first-degree relatives. More recently, with the identification of the genes responsible for most hereditary ovarian cancers (BRCA1, BRCA2), oophorectomy can now be offered specifically to women who are mutation carriers. Conversely, nonca rriers in these families can be reassured that their risk of ovarian cancer is not increased. The value of oophorectomy in mutation carriers has not yet been proven, how ever, and concern exists that the benefit may be less than intuitively expe cted. First, although the lifetime risk of ovarian cancer initially was rep orted to be as high as 60%, more recent studies have suggested risks in the range of 15 to 30%. A better understanding of the factors that underlie va riable penetrance in mutation carriers is needed to augment our ability to counsel individual women. In addition, peritoneal papillary serous carcinom a indistinguishable from ovarian cancer occurs in some women after oophorec tomy. Studies that better define the frequency with which this occurs are n eeded to establish the magnitude of the protective effect conferred by prop hylactic oophorectomy. In view of the uncertainty regarding the efficacy of prophylactic oophorect omy, chemopreventive and early detection approaches also deserve considerat ion as strategies for decreasing ovarian cancer mortality in women who carr y mutations in ovarian cancer susceptibility genes. Cancer 1999;86:2517-24. (C) 1999 American Cancer Society.