High-Grade Serous Carcinoma at Risk-Reducing Salpingo-Oophorectomy in Asymptomatic Carriers of <i>BRCA1/2</i> Pathogenic Variants: Prevalence and Clinical Factors.

Abstract

To investigate the prevalence of and clinical factors associated with high-grade serous carcinoma (HGSC) at risk-reducing salpingo-oophorectomy (RRSO) in asymptomatic <i>BRCA1/2</i>-pathogenic variant (PV) carriers. We included <i>BRCA1/2</i>-PV carriers who underwent RRSO between 1995 and 2018 from the Hereditary Breast and Ovarian cancer in the Netherlands study. All pathology reports were screened, and histopathology reviews were performed for RRSO specimens with epithelial abnormalities or where HGSC developed after normal RRSO. We then compared clinical characteristics, including parity and oral contraceptive pill (OCP) use, for women with and without HGSC at RRSO. Of the 2,557 included women, 1,624 had <i>BRCA1</i>, 930 had <i>BRCA2</i>, and three had both <i>BRCA1/2</i>-PV. The median age at RRSO was 43.0 years (range: 25.3-73.8) for <i>BRCA1</i>-PV and 46.8 years (27.6-77.9) for <i>BRCA2</i>-PV carriers. Histopathologic review confirmed 28 of 29 HGSCs and two further HGSCs from among 20 apparently normal RRSO specimens. Thus, 24 (1.5%) <i>BRCA1</i>-PV and 6 (0.6%) <i>BRCA2</i>-PV carriers had HGSC at RRSO, with the fallopian tube identified as the primary site in 73%. The prevalence of HGSC in women who underwent RRSO at the recommended age was 0.4%. Among <i>BRCA1/2-</i>PV carriers, older age at RRSO increased the risk of HGSC and long-term OCP use was protective. We detected HGSC in 1.5% (<i>BRCA1</i>-PV) and 0.6% (<i>BRCA2</i>-PV) of RRSO specimens from asymptomatic <i>BRCA1/2</i>-PV carriers. Consistent with the fallopian tube hypothesis, we found most lesions in the fallopian tube. Our results highlight the importance of timely RRSO with total removal and assessment of the fallopian tubes and show the protective effects of long-term OCP.