Prophylactic Salpingectomy and Delayed Oophorectomy as an Alternative for BRCA Mutation Carriers

Abstract

Young women with BRCA mutations are at high risk of ovarian and breast cancer and cancer-related mortality. To reduce the risk of ovarian cancer, it is recommended that these women undergo prophylactic bilateral salpingo-oophorectomy by the age of 40 years or on completion of childbearing. This early intervention decreases their risk of ovarian cancer by 80% to 90%, risk of breast cancer by 50%, and cancer-related mortality by about 60%. However, many women are reluctant to have prophylactic bilateral salpingo-oophorectomy at an early age, because of adverse consequences of estrogen deficiency, which include premature menopause, vasomotor symptoms, urogenital atrophy, and risk of osteoporosis and cardiovascular disease. No studies have directly compared prophylactic salpingectomy with bilateral salpingo-oophorectomy in this high-risk population. The observation that a high proportion of these carcinomas are invasive high-grade serous carcinomas of the fallopian tube or serous tubal intraepithelial carcinomas suggested that prophylactic bilateral salpingectomy may be an alternative to bilateral salpingo-oophorectomy and obviate the need for oophorectomy. The aim of this study was to compare the costs and benefits of salpingectomy with bilateral salpingo-oophorectomy for young women who carry BRCA mutations. A Markov Monte Carlo simulation model was developed to estimate the costs and benefits of the following 3 risk-reducing strategies in BRCA mutation carriers: (1) bilateral salpingo-oophorectomy at age 40 years; (2) bilateral salpingectomy at age 40 years; and (3) bilateral salpingectomy at age 40 years followed by delayed bilateral oophorectomy at age 50 years. The net health benefits of each strategy were estimated in years-of-life expectancy and quality-adjusted life-year expectancy. The primary study outcome was the incremental cost-effectiveness ratio. Average lifetime costs were calculated in Canadian dollars for the year 2012. For each strategy, the number of future breast and ovarian cancers and cardiovascular deaths attributed to premature menopause was estimated. Of the 3 strategies, bilateral salpingo-oophorectomy had the lowest cost and provided the highest life expectancy. However, with inclusion of quality-of-life measures in the model, salpingectomy followed by delayed oophorectomy yielded the highest quality-adjusted life expectancy and had incremental cost-effectiveness ratios of $37,805 and $89,680 per quality-adjusted life-year for BRCA1 and BRCA2, respectively, relative to salpingectomy alone. Bilateral salpingo-oophorectomy at age 40 years offered the greatest risk reduction against breast and ovarian cancer compared with the other 2 strategies. These data show that bilateral salpingo-oophorectomy provides the greatest risk reduction for breast and ovarian cancer among women with BRCA mutations compared with salpingectomy with or without delayed oophorectomy. However, when quality of life is considered, and bilateral salpingo-oophorectomy is unacceptable, bilateral salpingectomy with delayed oophorectomy is a cost-effective reasonable alternative.