{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T17:01:15Z","timestamp":1792515675684,"version":"4.5.0"},"reference-count":42,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"14","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2023,5,10]]},"abstract":"<jats:sec><jats:title>PURPOSE<\/jats:title><jats:p> 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. <\/jats:p><\/jats:sec><jats:sec><jats:title>PATIENTS AND METHODS<\/jats:title><jats:p> 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. <\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p> 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. <\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION<\/jats:title><jats:p> 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. <\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.22.01237","type":"journal-article","created":{"date-parts":[[2023,2,21]],"date-time":"2023-02-21T21:00:15Z","timestamp":1677013215000},"page":"2523-2535","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":16,"title":["High-Grade Serous Carcinoma at Risk-Reducing Salpingo-Oophorectomy in Asymptomatic Carriers of <i>BRCA1\/2<\/i> Pathogenic Variants: Prevalence and Clinical Factors"],"prefix":"10.1200","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5506-8841","authenticated-orcid":false,"given":"Iris A.S.","family":"Stroot","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands"},{"name":"Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Brouwer","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0985-071X","authenticated-orcid":false,"given":"Joost","family":"Bart","sequence":"additional","affiliation":[{"name":"Department of Pathology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry","family":"Hollema","sequence":"additional","affiliation":[{"name":"Department of Pathology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise J.","family":"Stommel-Jenner","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Netherlands Cancer Institute, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marise M.","family":"Wagner","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1062-4485","authenticated-orcid":false,"given":"Helena C.","family":"van Doorn","sequence":"additional","affiliation":[{"name":"Department of Gynecologic Oncology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne A.","family":"de Hullu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Radboud University Medical Center, Nijmegen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4702-1680","authenticated-orcid":false,"given":"Katja N.","family":"Gaarenstroom","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Leiden University Medical Center, Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Beurden","sequence":"additional","affiliation":[{"name":"Department of Gynecology, Antoni van Leeuwenhoek, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6905-2704","authenticated-orcid":false,"given":"Luc R.C.W.","family":"van Lonkhuijzen","sequence":"additional","affiliation":[{"name":"Department of Gynecologic Oncology, Amsterdam University Medical Center-Center for Gynecological Oncology Amsterdam, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brigitte F.M.","family":"Slangen","sequence":"additional","affiliation":[{"name":"Department of Gynecology, Maastricht University Medical Center, Maastricht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1829-7773","authenticated-orcid":false,"given":"Ronald P.","family":"Zweemer","sequence":"additional","affiliation":[{"name":"Department of Gynecologic Oncology, University Medical Center Utrecht, Utrecht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4999-8847","authenticated-orcid":false,"given":"Encarna B.","family":"G\u00f3mez Garcia","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, University Medical Center Maastricht, Maastricht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0305-3477","authenticated-orcid":false,"given":"Margreet G.E.M.","family":"Ausems","sequence":"additional","affiliation":[{"name":"Division Laboratories, Pharmacy and Biomedical Genetics, Department of Genetics, University Medical Center Utrecht, Utrecht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid A.","family":"Boere","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaartje","family":"van Engelen","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1436-7650","authenticated-orcid":false,"given":"Christi J.","family":"van Asperen","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2228-429X","authenticated-orcid":false,"given":"Marjanka K.","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Netherlands Cancer Institute, Amsterdam, the Netherlands"},{"name":"Department of Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands"},{"name":"Division of Molecular Pathology, Netherlands Cancer Institute, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8008-6008","authenticated-orcid":false,"given":"Marijke R.","family":"Wevers","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Radboud University Medical Center, Nijmegen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3104-4471","authenticated-orcid":false,"given":"Geertruida H.","family":"de Bock","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2385-2639","authenticated-orcid":false,"given":"Marian J.E.","family":"Mourits","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands"},{"name":"Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON), Coordinating Center: Netherlands Cancer Institute, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on behalf of the HEBON Investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"b1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2006.09.1066"},{"key":"b2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2017.7112"},{"key":"b3","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20040952"},{"key":"b4","doi-asserted-by":"publisher","DOI":"10.1186\/s12935-021-02295-y"},{"key":"b5","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2012.07.021"},{"key":"b6","doi-asserted-by":"publisher","DOI":"10.1097\/01.pas.0000213335.40358.47"},{"key":"b7","doi-asserted-by":"publisher","DOI":"10.3121\/cmr.2007.702"},{"key":"b8","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2016.238"},{"key":"b9","doi-asserted-by":"publisher","DOI":"10.1002\/path.1000"},{"key":"b10","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6603725"},{"key":"b11","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.24038"},{"key":"b12","doi-asserted-by":"publisher","DOI":"10.1186\/s12905-014-0150-5"},{"key":"b13","doi-asserted-by":"publisher","DOI":"10.1097\/00000478-200110000-00009"},{"key":"b14","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0000000000003702"},{"key":"b15","doi-asserted-by":"publisher","DOI":"10.3802\/jgo.2017.28.e3"},{"key":"b16","doi-asserted-by":"publisher","DOI":"10.1006\/gyno.2002.6779"},{"key":"b17","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.04.109"},{"key":"b18","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2006.03.006"},{"key":"b19","doi-asserted-by":"publisher","DOI":"10.1158\/1940-6207.CAPR-18-0009"},{"key":"b20","doi-asserted-by":"publisher","DOI":"10.1097\/IGC.0b013e31821bc7e3"},{"key":"b21","doi-asserted-by":"publisher","DOI":"10.1097\/CEJ.0000000000000217"},{"key":"b22","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djv033"},{"key":"b23","first-page":"19","volume":"29","author":"Casparie M","year":"2007","journal-title":"Cell Oncol"},{"key":"b24","volume-title":"Erfelijk en familiair ovariumcarcinoom","author":"Federatie Medisch Specialisten"},{"key":"b25","doi-asserted-by":"publisher","DOI":"10.1097\/01.pas.0000180854.28831.77"},{"key":"b26","first-page":"695","volume-title":"Arch Gynecol Obstet","volume":"293","author":"Meinhold-Heerlein I","year":"2016"},{"key":"b27","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejogrb.2014.10.003"},{"key":"b28","doi-asserted-by":"publisher","DOI":"10.1002\/cjp2.53"},{"key":"b29","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2013.54.1987"},{"key":"b30","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2019.03.003"},{"key":"b31","doi-asserted-by":"publisher","DOI":"10.1097\/IGC.0b013e31822d0e91"},{"key":"b32","doi-asserted-by":"publisher","DOI":"10.1158\/1940-6207.CAPR-10-0266"},{"key":"b33","doi-asserted-by":"publisher","DOI":"10.1097\/PGP.0000000000000120"},{"key":"b34","doi-asserted-by":"publisher","DOI":"10.1002\/path.1817"},{"key":"b35","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2021.1590"},{"key":"b36","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-015-1597-y"},{"key":"b37","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-08-0112"},{"key":"b38","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2013.53.2820"},{"key":"b39","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2021.01.014"},{"key":"b40","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2019.01.061"},{"key":"b41","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgv132"},{"key":"b42","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djac004"}],"container-title":["Journal of Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/JCO.22.01237","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,5]],"date-time":"2023-05-05T22:01:51Z","timestamp":1683324111000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO.22.01237"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,10]]},"references-count":42,"journal-issue":{"issue":"14","published-print":{"date-parts":[[2023,5,10]]}},"alternative-id":["10.1200\/JCO.22.01237"],"URL":"https:\/\/doi.org\/10.1200\/jco.22.01237","relation":{},"ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,10]]},"assertion":[{"value":"2022-05-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-12-21","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-01-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-02-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}