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.

Cost-Effectiveness of Risk-Reducing Surgery for Breast and Ovarian Cancer Prevention: A Systematic Review

“…Similarly, risk-reducing salpingo-oophorectomy (RRSO) is the gold-standard preventive strategy for OC [ 15 ]. RRSO provides a risk reduction of up to 97% [ 15 , 16 , 17 ]. While it has previously been offered to women with an estimated ≥10% lifetime OC risk, it is now recommended at >4–5% lifetime OC-risk, including women with moderate-penetrance CSGs [ 18 , 19 , 20 ].…”

Quality of life after risk-reducing surgery for breast and ovarian cancer prevention: a systematic review and meta-analysis

“…RRSO is the gold-standard OC preventive strategy, reducing OC-risk by 80-97%. [29][30][31] RRSO has been undertaken for BRCA1/BRCA2 carriers, or women with a strong FH of OC. Broadening access has led to RRSO now being offered to women at >4-5% lifetime OC-risk, including newer moderate-penetrance OC CSGs and women with a first-degree-relative with high-grade serous OC.…”

Emodin exerts antitumor effects in ovarian cancer cell lines by preventing the development of cancer stem cells via epithelial mesenchymal transition

“…With the advancement of medical technology, debulking surgery and cis-platinum-based chemotherapy are the major therapeutics for ovarian cancer. However, the outcome of debulking surgery is dependent on surgical skill and the genetic features of the tumor ( 4 , 5 ). Debulking surgery combined with cis-platinum based chemotherapy can lead to remission in patients with ovarian cancer; however, the majority of patients suffer from cancer resistance, metastasis and relapse ( 6 , 7 ).…”