High-grade serous ovarian cancer after bilateral salpingo-oophorectomy

Extract

High-grade serous ovarian cancer (HGSOC) has a high heritable proportion, with a 3-fold increase in risk of developing the disease in women with first-degree relatives with HGSOC.¹ Carriers (heterozygotes) for germline pathogenic variants (GPVs) in BRCA1 or BRCA2 have a substantial lifetime risk of ovarian cancer, which is predominantly HGSOC.² Women with BRCA1/BRCA2 GPVs have a cumulative lifetime risk of epithelial non-mucinous ovarian cancer of 44%-61% and 17%-27%, respectively.^3-5 Female GPV heterozygotes in BRCA1/BRCA2 are strongly advised to undergo risk reducing bilateral salpingo-oophorectomy (RRBSO).⁶ RRBSO is usually encouraged at or just before the main uplift in ovarian cancer risk at 35-40 years for BRCA1 GPV heterozygotes and 40-45 years for BRCA2 GPV heterozygotes.^7,8 Female PV heterozygotes for BRCA1/2 undertaking RRBSO have improved life expectancy mainly due to reduction in ovarian cancer risk, with some potential reduction in breast cancer incidence and reduced mortality from previous breast cancer.^9-11

Women undergoing RRBSO are counseled about a residual risk of high-grade serous primary peritoneal cancer (HGSPPC), which was first reported in 1982.¹² A meta-analysis of studies assessing this risk suggested only a 79% reduction in risk of an “ovarian” type HGSPPC after RRBSO in BRCA1/2 GPV heterozygotes¹³ (hazard ratio [HR] 0.21; 95% CI = 0.12 to 0.39), although the incidence of HGSPPC may have been increased by reporting bias in some of the studies. Subsequent studies found that the likelihood of HGSPPC may be prevented by earlier surgery and was predominantly seen for BRCA1 GPV heterozygotes.¹⁴ The origin of HGSPPC has been hypothesized to be due to one of three potential sources. Firstly, that “ovarian rest cells” displaced during the embryological voyage in the abdominal cavity may be a primary origin. Secondly, that cells from the fimbria/ovaries could be displaced during adulthood into the peritoneal cavity, or thirdly through dissemination at the time of RRBSO. The latter 2 theories have become more prominent since the description of serous tubal in situ carcinoma (STIC) lesions in the fimbrial end of the fallopian tubes as the probable precursor lesion for most HGSOC/tubal cancers.¹⁵ Indeed, STIC lesions at RRBSO were predictive of subsequent HGSPPC in a single institution study with 2/7 (28.6%) developing Primary Peritoneal Cancer (PPC) after RRBSO compared to only 1/287 (0.3%) without STIC.¹⁶