In a Dutch study reported in the Journal of Clinical Oncology, Stroot et al identified the prevalence of high-grade serous carcinoma at risk-reducing salpingo-oophorectomy in asymptomatic BRCA1/2 pathogenic variant carriers.
Study Details
The study included asymptomatic BRCA1/2 pathogenic variant carriers who underwent risk-reducing salpingo-oophorectomy between 1995 and 2018 from the prospective Hereditary Breast and Ovarian cancer in the Netherlands (HEBON) study. All pathology reports were screened, and histopathology reviews were performed for risk-reducing salpingo-oophorectomy specimens with epithelial abnormalities or when high-grade serous carcinoma developed after normal risk-reducing salpingo-oophorectomy.
Key Findings
Among the 2,557 patients included in the analysis, 1,624 had BRCA1, 930 had BRCA2, and 3 had BRCA1 and BRCA2 pathogenic variants. Median age at risk-reducing salpingo-oophorectomy was 43.0 years (range = 25.3–73.8 years) for BRCA1 carriers and 46.8 years (range = 27.6–77.9 years) for BRCA2 carriers.
Histopathologic review confirmed that 30 of the 2,557 patients had high-grade serous carcinoma at risk-reducing salpingo-oophorectomy—a prevalence of 1.2% (95% confidence interval [CI] = 0.7%–1.6%). High-grade serous carcinoma was found in 24 BRCA1 carriers, a prevalence of 1.5% (95% CI = 0.9%–2.1%), and in 6 BRCA2 carriers, a prevalence of 0.6% (95% CI = 0.1%–1.1%).
The prevalence of high-grade serous carcinoma was 0.4% among 891 patients who underwent risk-reducing salpingo-oophorectomy at the recommended age (ie, 35–40 years for BRCA1 and 40–45 years for BRCA2 carriers), with high-grade serous carcinoma found in 3 (0.6%) of 508 BRCA1 carriers and 1 (0.3%) of 382 BRCA2 carriers. Among the 1,667 patients who underwent risk-reducing salpingo-oophorectomy after the recommended age, the prevalence of high-grade serous carcinoma was 1.5%; high-grade serous carcinoma was found in 21 (1.8%) of 1,119 BRCA1 carriers and in 5 (0.9%) of 548 BRCA2 carriers.
Among the 30 patients with high-grade serous carcinoma, the primary location was the fallopian tubes in 22 (73%), with 17 having lesions in the fallopian tubes only and 5 in both the fallopian tubes and ovaries. Lesions in the fallopian tubes were predominantly in the distal fallopian tubes or fimbriae. High-grade serous carcinoma was found in the ovaries alone in eight patients.
Patients with high-grade serous carcinoma were significantly older than those without: median age = 52.6 vs 43.2 years for BRCA1 carriers (P < .001; odds ratio [OR] = 1.09 per year, 95% CI = 1.04–1.14); and median age = 63.2 vs 47.3 years (P < .01) for BRCA2 carriers.
Longer oral contraceptive pill use was found to be protective. In the BRCA1 carrier group, more patients with vs without high-grade serous carcinoma reported never using oral contraceptive pills (16.7% vs 4.4%, P = .02; OR = 0.27, 95% CI = 0.09–0.84). Patients with high-grade serous carcinoma used oral contraceptive pills for shorter median durations than those without high-grade serous carcinoma: 8 vs 12 years among BRCA1 carriers (P = .001; OR = 0.89 per year, 95% CI = 0.8–-0.96); and 5 vs 12 years among BRCA2 carriers (P = .04).
The investigators concluded, “We detected high-grade serous carcinoma in 1.5% (BRCA1- pathogenic variant) and 0.6% (BRCA2-pathogenic variant) of risk-reducing salpingo-oophorectomy specimens from asymptomatic BRCA1/2 pathogenic variant carriers. Consistent with the fallopian tube hypothesis [ie, that the fallopian tubes represent a major origin site for high-grade serous carcinoma], we found most lesions in the fallopian tube. Our results highlight the importance of timely risk-reducing salpingo-oophorectomy with total removal and assessment of the fallopian tubes and show the protective effects of long-term oral contraceptive pill [use].”
Disclosure: The study was supported by the W.J. Thijn Stichting, Dutch Cancer Society, and others. For full disclosures of the study authors, visit ascopubs.org.
