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

Iris A S Stroot, Jan Brouwer, HEBON Investigators, Joost Bart, Harry Hollema, Denise J Stommel-Jenner, Marise M Wagner, Helena C van Doorn, Joanne A de Hullu, Katja N Gaarenstroom, Marc Beurden, Luc R C W van Lonkhuijzen, Brigitte F M Slangen, Ronald P Zweemer, Encarna B Gómez Garcia, Margreet G E M Ausems, Ingrid A Boere, Klaartje van Engelen, Christi J van Asperen, Marjanka K SchmidtMarijke R Wevers, Geertruida H de Bock, Marian J E Mourits*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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PURPOSE: To investigate the prevalence of and clinical factors associated with high-grade serous carcinoma (HGSC) at risk-reducing salpingo-oophorectomy (RRSO) in asymptomatic BRCA1/2-pathogenic variant (PV) carriers.

PATIENTS AND METHODS: We included BRCA1/2-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.

RESULTS: Of the 2,557 included women, 1,624 had BRCA1, 930 had BRCA2, and three had both BRCA1/2-PV. The median age at RRSO was 43.0 years (range: 25.3-73.8) for BRCA1-PV and 46.8 years (27.6-77.9) for BRCA2-PV carriers. Histopathologic review confirmed 28 of 29 HGSCs and two further HGSCs from among 20 apparently normal RRSO specimens. Thus, 24 (1.5%) BRCA1-PV and 6 (0.6%) BRCA2-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 BRCA1/2-PV carriers, older age at RRSO increased the risk of HGSC and long-term OCP use was protective.

CONCLUSION: We detected HGSC in 1.5% (BRCA1-PV) and 0.6% (BRCA2-PV) of RRSO specimens from asymptomatic BRCA1/2-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.

Original languageEnglish
Pages (from-to)2523-2535
Number of pages13
JournalJournal of clinical oncology : official journal of the American Society of Clinical Oncology
Issue number14
Early online date21 Feb 2023
Publication statusPublished - 10 May 2023

Bibliographical note

Funding Information:
Supported by the W.J. Thijn Stichting. The HEBON study was supported by the Dutch Cancer Society grants NKI1998-1854, NKI2004-3088, and NKI2007-3756; the Netherlands Organisation of Scientific Research grant NWO 91109024; the Pink Ribbon grants 110005 and 2014-187.WO76; the BBMRI grant NWO 184.021.007/CP46; and the Transcan grant JTC 2012 Cancer 12-054.

Publisher Copyright:
© American Society of Clinical Oncology.


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