TY - JOUR
T1 - High-grade serous carcinoma occurring after risk-reducing salpingo-oophorectomy in BRCA1/2 germline pathogenic variant carriers
AU - HEBON Investigators
AU - Stroot, Iris A S
AU - Bart, Joost
AU - Hollema, Harry
AU - Wagner, Marise M
AU - Yigit, Refika
AU - van Doorn, Helena C
AU - de Hullu, Joanne A
AU - Gaarenstroom, Katja N
AU - van Beurden, Marc
AU - van Lonkhuijzen, Luc R C W
AU - Slangen, Brigitte F M
AU - Zweemer, Ronald P
AU - Gómez Garcia, Encarna B
AU - Ausems, Margreet G E M
AU - Komdeur, Fenne L
AU - van Asperen, Christi J
AU - Adank, Muriel A
AU - Wevers, Marijke R
AU - Hooning, Maartje J
AU - Mourits, Marian J E
AU - de Bock, Geertruida H
N1 - © The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: [email protected].
PY - 2025/4
Y1 - 2025/4
N2 - BACKGROUND: Risk-reducing salpingo-oophorectomy (RRSO) effectively prevents high-grade serous carcinoma (HGSC) in BRCA1/2 germline pathogenic variant (GPV) carriers. Still, some women develop HGSC after RRSO without pathologic findings. This study assessed long-term incidence and risk factors for developing HGSC after RRSO without pathologic findings.METHODS: BRCA1/2 GPV carriers were selected from Hereditary Breast and Ovarian cancer in the Netherlands (HEBON) cohort. Follow-up data for HGSC after RRSO were obtained from the Dutch Nationwide Pathology Databank (PALGA) and confirmed by histopathological review. Cumulative incidence rates of HGSC were calculated using Kaplan-Meier analyses. Cox proportional hazards model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for factors associated with an increased risk of HGSC following RRSO without pathologic findings.RESULTS: A total of 2519 women were included, with a median follow-up of 13.4 years (range: 0.0-27.6). The 20-years cumulative incidence rate of HGSC was 1.5% (95% CI: 0.0-2.1) for BRCA1 and 0.2% (95% CI: 0.0-1.4) for BRCA2 GPV carriers. All women who developed HGSC underwent RRSO after the recommended age. Incomplete embedding of the RRSO specimen (HR: 4.2, 95% CI: 1.4-12.6), higher age at RRSO (HR per year: 1.1, 95% CI: 1.0-1.1), and carrying a BRCA1 GPV (HR: 12.1, 95% CI: 1.6-91.2) were associated with increased risk of HGSC.CONCLUSIONS: In BRCA1/2 GPV carriers, long-term incidence of HGSC after RRSO without pathologic findings was low. Strict adherence to guidelines regarding timely RRSO followed by complete specimen embedding can further reduce the risk of HGSC in the years following RRSO.
AB - BACKGROUND: Risk-reducing salpingo-oophorectomy (RRSO) effectively prevents high-grade serous carcinoma (HGSC) in BRCA1/2 germline pathogenic variant (GPV) carriers. Still, some women develop HGSC after RRSO without pathologic findings. This study assessed long-term incidence and risk factors for developing HGSC after RRSO without pathologic findings.METHODS: BRCA1/2 GPV carriers were selected from Hereditary Breast and Ovarian cancer in the Netherlands (HEBON) cohort. Follow-up data for HGSC after RRSO were obtained from the Dutch Nationwide Pathology Databank (PALGA) and confirmed by histopathological review. Cumulative incidence rates of HGSC were calculated using Kaplan-Meier analyses. Cox proportional hazards model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for factors associated with an increased risk of HGSC following RRSO without pathologic findings.RESULTS: A total of 2519 women were included, with a median follow-up of 13.4 years (range: 0.0-27.6). The 20-years cumulative incidence rate of HGSC was 1.5% (95% CI: 0.0-2.1) for BRCA1 and 0.2% (95% CI: 0.0-1.4) for BRCA2 GPV carriers. All women who developed HGSC underwent RRSO after the recommended age. Incomplete embedding of the RRSO specimen (HR: 4.2, 95% CI: 1.4-12.6), higher age at RRSO (HR per year: 1.1, 95% CI: 1.0-1.1), and carrying a BRCA1 GPV (HR: 12.1, 95% CI: 1.6-91.2) were associated with increased risk of HGSC.CONCLUSIONS: In BRCA1/2 GPV carriers, long-term incidence of HGSC after RRSO without pathologic findings was low. Strict adherence to guidelines regarding timely RRSO followed by complete specimen embedding can further reduce the risk of HGSC in the years following RRSO.
U2 - 10.1093/jnci/djae300
DO - 10.1093/jnci/djae300
M3 - Article
C2 - 39579093
SN - 0027-8874
VL - 117
SP - 719
EP - 727
JO - Journal of the National Cancer Institute
JF - Journal of the National Cancer Institute
IS - 4
ER -