Genetic susceptibility testing and prophylactic oophorectomy

About 10% of ovarian cancer cases are thought to have a hereditary basis an d family history is the strongest risk factor for the development of this d isease. In the past, prophylactic oophorectomy 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, non-carriers in these families can be re assured that their risk of ovarian cancer is not increased. The value of oo phorectomy in mutation carriers has not yet been proven, however, and there are concerns that the benefit may be less than intuitively expected. First , although the lifetime risk of ovarian cancer initially was reported to be as high as 60%, more recent studies have reported risks in the range of 15 -30%. A better understanding of the genetic and/or environmental basis of v ariable penetrance is needed to augment our ability to counsel women regard ing their risk. In addition, peritoneal papillary serous carcinoma indistin guishable from ovarian cancer occurs in some women following oophorectomy. Studies that better define how often this occurs also are needed to establi sh more firmly the value of prophylactic oophorectomy. In view of the uncer tainty regarding the efficacy of prophylactic oophorectomy, chemopreventive and early detection approaches also deserve consideration as strategies fo r decreasing ovarian cancer mortality in women who carry mutations in ovari an cancer susceptibility genes. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.