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.
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.
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.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.