Specialist oncological surgery for removal of the ovaries and fallopian tubes in BRCA1 and BRCA2 pathogenic variant carriers may reduce primary peritoneal cancer risk to very low levels

Abstract

Risk-reducing bilateral salpingo-oophorectomy (RRBSO) is highly effective for the prevention of high-grade serous ovarian cancer (HGSOC) in BRCA1/2 pathogenic variant carriers (PVCs), but does not completely eliminate future risk of primary peritoneal cancer (PPC). The requirement to completely remove fallopian tubes at RRBSO and carefully exclude occult cancer/serous tubal intraepithelial carcinoma (STIC) lesions may not have been appreciated historically. We calculated rates of HGSOC and PPC in confirmed BRCA1/2 PVCs registered on the regional database in those who did (cases) and did not (controls) undergo RRBSO after genetic testing. Expected annual rates of ovarian/peritoneal cancer were 1% for BRCA1 ≥ 35 years and 0.5% for BRCA2 ≥ 45 years. Follow-up before 35/45 years was "risk free" and lead time excluded RRBSO <35 years and <45 years for BRCA1 and BRCA2, respectively. Women were followed from personal mutation report (controls) or RRBSO (cases) to death, ovarian/peritoneal cancer or last follow-up, whichever was sooner. In total, 891 cases (BRCA1 = 468, BRCA2 = 423) and 1302 controls had follow-up ≥35 years (BRCA1 = 736) and ≥45 years (BRCA2 = 566), respectively, over a total of 7261.1 risk eligible years (mean = 8.15 years). Twenty-one occult ovarian cancers were found at RRBSO (2.4%), 16 at stage 1. Post RRBSO, 56.97 ovarian/peritoneal cancers were expected but only 3 were observed (HR = 0.053; 95% CI = 0.013-0.14), with combined Kaplan-Meier analysis HR = 0.029 (95% CI = 0.009-0.100, P < .001). Risk reduction was greater in specialist (HR = 0.03; 95% CI = 0.001-0.13) compared to non-specialist centres (HR = 0.11; 95% CI = 0.02-0.37) (P = .07). In controls, 23.35 ovarian/peritoneal cancers were expected with 32 observed (HR = 1.37; 95% CI = 0.95-1.91). RRBSO <35/<45 years reduces the risk of ovarian/peritoneal cancer by 95% in BRCA1/2 PVCs and may be greater in specialist centres.