Quality or Quantity in the Management of Hereditary Ovarian Cancer Risk: Is It Really a Trade-Off?

Abstract

Women with increased probability of developing ovarian cancer face the dilemma of how best to manage their risk. Lifetime ovarian cancer risk is increased in women who carry germline mutations in the hereditary breastovarian cancer susceptibility genes BRCA1 (40% to 60%) and BRCA2 (15% to 20%), 1 and in the hereditary nonpolyposis colon cancer–associated genes (10% to 12% risk), 2 as well as in familial clusters not attributable to known genes. Current options for early detection of ovarian cancer include serial transvaginal ultrasound examinations and serum CA-125 determinations, but the sensitivity of these methods remains disappointing. 3 Risk-reducing salpingooophorectomy (RRSO) has been shown to reduce the risk of ovarian and fallopian tube cancers in women with BRCA1/2 mutations by more than 90%. 4,5 When performed in premenopausal BRCA1/2 mutation carriers, RRSO also reduces the risk of breast cancer by nearly 50%, 4,5 consistent with older data documenting a substantial reduction in breast cancer risk in normal-risk women conferred by surgical menopause before age 40 years. 6 Based on such data, RRSO is recommended by several groups for BRCA1/2 mutation carriers following completion of child-bearing after age 35 to 40 years. 7,8 However, medical management strategies remain suboptimal for the consequences of premature menopause, including vasomotor symptoms, and sexual and skeletal health. Therefore, premenopausal women with high ovarian cancer risk must prepare to take on early menopause as the very significant price of effective risk reduction. In this issue of the Journal of Clinical Oncology, Madalinska et al 9 present a snapshot of the quality of life (QOL) among high-risk women who have undergone RRSO, compared with those who are relying on surveillance to manage their increased ovarian cancer risk. In their cross-sectional study, the investigators used mailed surveys to collect data from women identified from gynecologic practices across the Netherlands who had increased ovarian cancer risk because of hereditary familial breast and ovarian cancer syndrome. The analysis was conducted on a large sample of 846 high-risk women, among whom 369 (44%) had undergone RRSO, while 477 (56%) were following surveillance programs (pelvic examination, transvaginal sonography, and serum CA-125 determination). A number of validated QOL measures were included in the instrument. The findings should be reassuring to women considering prophylactic surgery. Overall QOL measured using four of eight subscales of the SF36 Health Survey was not different between the two groups. Women who had undergone surgery had less cancer worry (P .001), and in multivariate analysis, less specific worry about ovarian cancer risk (P .001) for themselves and their family members (P .0001) than did women who had chosen screening. However, women who had chosen surgery also reported significantly more endocrine symptoms and sexual dysfunction than women who had opted for gynecologic screening, despite similar levels of sexual activity, and also despite hormone therapy. Finally, 97% of women who had undergone RRSO reported satisfaction with surgery, while 33% of the women in the surveillance group reported their intention to have surgery in the future. The authors recommend that counseling for women about prophylactic ovarian surgery include both reassurance that most women report good QOL after surgery, with relief from cancer worry, and caution that menopause symptoms will often be problematic. The findings of Mandalinska et al are consistent with the existing literature 10-12 and will resonate with providers caring for women facing these decisions. A significant strength of this study compared with prior reports is the