Impact of Oophorectomy on Cancer Incidence and Mortality in Women With a BRCA1 or BRCA2 Mutation

Abstract

Purpose The purposes of this study were to estimate the reduction in risk of ovarian, fallopian tube, or peritoneal cancer in women with a BRCA1 or BRCA2 mutation after oophorectomy, by age of oophorectomy; to estimate the impact of prophylactic oophorectomy on all-cause mortality; and to estimate 5-year survival associated with clinically detected ovarian, occult, and peritoneal cancers diagnosed in the cohort. Patients and Methods Women with a BRCA1 or BRCA2 mutation were identified from an international registry; 5,783 women completed a baseline questionnaire and ≥ one follow-up questionnaires. Women were observed until either diagnosis of ovarian, fallopian tube, or peritoneal cancer, death, or date of most recent follow-up. Hazard ratios (HRs) for cancer incidence and all-cause mortality associated with oophorectomy were evaluated using time-dependent survival analyses. Results After an average follow-up period of 5.6 years, 186 women developed either ovarian (n = 132), fallopian (n = 22), or peritoneal (n = 32) cancer, of whom 68 have died. HR for ovarian, fallopian, or peritoneal cancer associated with bilateral oophorectomy was 0.20 (95% CI, 0.13 to 0.30; P < .001). Among women who had no history of cancer at baseline, HR for all-cause mortality to age 70 years associated with an oophorectomy was 0.23 (95% CI, 0.13 to 0.39; P < .001). Conclusion Preventive oophorectomy was associated with an 80% reduction in the risk of ovarian, fallopian tube, or peritoneal cancer in BRCA1 or BRCA2 carriers and a 77% reduction in all-cause mortality.

Risk-reducing surgery in hereditary gynecological cancer: Clinical applications in Lynch syndrome and hereditary breast and ovarian cancer

“…This led to the recommendation that BRCA1 mutation carriers should undergo RRSO by the age of 35 years. Finch et al (17) also observed that the rate of diagnosis of ovarian cancer was 4.0% if a BRCA1 mutation carrier chose to delay RRSO until the age of 40 years and that this rate increased to 14.2% with a delay until the age of 50 years.…”

“…King et al (16) observed that the risk of developing ovarian and breast cancer at the age of 40, 50 and 60 years was 3, 21 and 40%, respectively, in BRCA1 mutation carriers and 2, 2 and 6%, respectively, in BRCA2 mutation carriers; they also reported that the risk of developing breast cancer at these ages was 21, 39 and 58%, respectively, in BRCA1 mutation carriers and 17, 34 and 48%, respectively, in BRCA2 mutation carriers. Finch et al (17) reported that the prevalence of occult carcinoma was 1.5% for BRCA1 mutation carriers who underwent oophorectomy at <40 years of age and 3.8%…”

“…Over a mean follow-up period of 3 years, the overall mortality was also found to be reduced in patients who underwent RRSO compared to those who did not (3 vs. 10%, respectively) (36). Finch et al (17) observed 5,783 women with a BRCA1 or BRCA2 mutation prospectively for an average of 5.6 years and reported hazard ratios for all-cause mortality following RRSO of 0.30 (95% CI: 0.24-0.38) and 0.33 (95% CI: 0.22-0.50) for BRCA1 and BRCA2 mutation carriers, respectively.…”

“…A mean of 5.3 years had elapsed between RRSO and cancer diagnosis (median, 3 years). Finch et al (17) estimated the risk of peritoneal cancer in the 20 years following RRSO to be 3.9% for BRCA1 and 1.9% for BRCA2 mutation carriers. A proportion of these cases were metastases of subclinical disease present at the time of surgery and, thus, the authors recommended earlier RRSO to prevent peritoneal cancer.…”

Legislation in the genomic era: the Affordable Care Act and genetic testing for cancer risk assessment

“…This risk decreases considerably after prophylactic salpingo-oophorectomy and has substantial mortality benefits in BRCA1/2 mutation carriers. 8 In light of these considerations the ACA section 2713 may benefit from expanded provisions for genetic testing as a preventive service for individuals with a previous diagnosis of cancer.…”