{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T18:56:55Z","timestamp":1790535415196,"version":"4.1.0"},"reference-count":39,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:00:00Z","timestamp":1790467200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:00:00Z","timestamp":1790467200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Prostate"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      The clinical characteristics of\n                      <jats:italic>BRCA1<\/jats:italic>\n                      and\n                      <jats:italic>BRCA2<\/jats:italic>\n                      (\n                      <jats:italic>BRCA<\/jats:italic>\n                      ) deleterious alterations in advanced prostate cancer\u2014considering age, family history, co\u2010occurring gene alterations, and variant type\u2014remain incompletely understood in patients undergoing tumor\u2010only panel testing.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>We analyzed 2,815 patients who underwent comprehensive cancer genomic profiling (CGP) using a tissue\u2010based tumor\u2010only panel from December 2020 to November 2024. Eligible patients had metastatic prostate cancer resistant to standard therapies or androgen\u2010indifferent prostate cancer, including neuroendocrine prostate cancer. Data were obtained from the Center for Cancer Genomics and Advanced Therapeutics, a nationwide CGP database in Japan.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Median age at CGP testing was 72 years (range 23\u201393 years).\n                      <jats:italic>BRCA<\/jats:italic>\n                      deleterious alterations were detected in 428 patients (15.2%), decreasing with age: 24.2% (&lt;\u200950 years), 25.4% (50\u201359 years), 16.3% (60\u201369 years), 14.3% (70\u201379 years), and 9.3% (\u2265\u200980 years). A family history of breast or ovarian cancer independently predicted\n                      <jats:italic>BRCA<\/jats:italic>\n                      alterations (odds ratio 1.901 and 3.016; both\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05).\n                      <jats:italic>RB1<\/jats:italic>\n                      alterations and\n                      <jats:italic>MYC<\/jats:italic>\n                      amplification were significantly enriched as co\u2010occurring alterations in\n                      <jats:italic>BRCA2<\/jats:italic>\n                      (6.9% vs. 14.9%, 15.4% vs. 23.1%; both\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). Stratified by\n                      <jats:italic>BRCA2<\/jats:italic>\n                      variant type, patients with homozygous deletion (HD) had longer overall survival than those with truncating alterations following olaparib treatment (median 30.6 vs. 16.9 months; hazard ratio 0.373; 95% CI 0.220\u20130.633).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      In advanced, therapy\u2010resistant prostate cancer,\n                      <jats:italic>BRCA<\/jats:italic>\n                      deleterious alterations were more frequent in younger patients and those in with a family history of breast and ovarian cancer.\n                      <jats:italic>BRCA2<\/jats:italic>\n                      HD was significantly associated with a favorable response to olaparib.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pros.70260","type":"journal-article","created":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T18:45:09Z","timestamp":1790534709000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Real\u2010World Landscape of\n                    <i>BRCA<\/i>\n                    Deleterious Alterations in Advanced Prostate Cancer: Insights From a Nationwide Genomic Database"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8962-2345","authenticated-orcid":false,"given":"Hideyasu","family":"Tsumura","sequence":"first","affiliation":[{"name":"Department of Urology Kitasato University School of Medicine Sagamihara Japan"},{"name":"Genetics Division, Department of Genetics Kitasato University Hospital Sagamihara 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Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6851-8665","authenticated-orcid":false,"given":"Shuhei","family":"Hirano","sequence":"additional","affiliation":[{"name":"Department of Urology Kitasato University School of Medicine Sagamihara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1017-9799","authenticated-orcid":false,"given":"Masaomi","family":"Ikeda","sequence":"additional","affiliation":[{"name":"Department of Urology Kitasato University School of Medicine Sagamihara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takefumi","family":"Satoh","sequence":"additional","affiliation":[{"name":"Department of Urology Kitasato University School of Medicine Sagamihara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiko","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Genetics Division, Department of Genetics Kitasato University Hospital Sagamihara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomi","family":"Araki","sequence":"additional","affiliation":[{"name":"Genetics Division, Department of Genetics Kitasato University Hospital Sagamihara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2434-8023","authenticated-orcid":false,"given":"Akinori","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Kitasato University School of Medicine Sagamihara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsutomu","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Division of Molecular Pathology, Department of Comprehensive Medicine Research and Development Center for New Medical Frontiers, Kitasato University School of Medicine Sagamihara 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Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9465-5161","authenticated-orcid":false,"given":"Kazumasa","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Department of Urology Kitasato University School of Medicine Sagamihara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,27]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"crossref","first-page":"1748","DOI":"10.1200\/JCO.2012.43.1882","article-title":"Germline BRCA Mutations Are Associated With Higher Risk of Nodal Involvement, Distant Metastasis, and Poor Survival Outcomes in Prostate Cancer","volume":"31","author":"Castro E.","year":"2013","journal-title":"Journal of Clinical Oncology"},{"key":"e_1_2_10_3_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.ebiom.2023.104738","article-title":"BRCA\u2010Deficient Metastatic Prostate Cancer Has an Adverse Prognosis and Distinct Genomic 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J.","year":"2024","journal-title":"European Urology Oncology"}],"container-title":["The Prostate"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pros.70260","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/pros.70260","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pros.70260","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T18:45:14Z","timestamp":1790534714000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pros.70260"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,27]]},"references-count":39,"alternative-id":["10.1002\/pros.70260"],"URL":"https:\/\/doi.org\/10.1002\/pros.70260","archive":["Portico"],"relation":{},"ISSN":["0270-4137","1097-0045"],"issn-type":[{"value":"0270-4137","type":"print"},{"value":"1097-0045","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,27]]},"assertion":[{"value":"2026-05-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"pros.70260"}}