{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T12:56:27Z","timestamp":1768568187249,"version":"3.49.0"},"posted":{"date-parts":[[2025,3,3]]},"group-title":"Oncology","reference-count":30,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,3,3]],"date-time":"2025-03-03T00:00:00Z","timestamp":1740960000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,3,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Breast cancer is multifactorial. Focusing on limited risk factors may miss high-risk individuals.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>\n                    We assessed the performance and overlap of various risk factors in identifying high-risk individuals for invasive breast cancer (BrCa) and ductal carcinoma in situ (DCIS) in 161,849 European-ancestry and 18,549 Asian-ancestry women. Discriminatory ability was evaluated using the area under the receiver operating characteristic curve (AUC). High-risk criteria included: 5-year absolute risk \u22651\u00b766% by the Gail model [GAIL\n                    <jats:sub>binary<\/jats:sub>\n                    ]; first-degree family history of breast cancer [FH\n                    <jats:sub>binary<\/jats:sub>\n                    ]; 5-year absolute risk \u22651\u00b766% by a 313-variants polygenic risk score [PRS\n                    <jats:sub>binary<\/jats:sub>\n                    ]; and carriers of pathogenic variants in breast cancer predisposition genes [PTV\n                    <jats:sub>binary<\/jats:sub>\n                    ].\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Findings<\/jats:title>\n                  <jats:p>\n                    The 5-year absolute risk by PRS outperformed the Gail model in predicting BrCa (Europeans\n                    <jats:sub>vs<\/jats:sub>\n                    <jats:sub>controls<\/jats:sub>\n                    : AUC\n                    <jats:sub>PRS<\/jats:sub>\n                    =0\u00b7635 [0\u00b7632-0\u00b7638] vs AUC\n                    <jats:sub>Gail<\/jats:sub>\n                    =0\u00b7492 [0\u00b7489-0\u00b7495]; Asians\n                    <jats:sub>vs<\/jats:sub>\n                    <jats:sub>controls<\/jats:sub>\n                    : AUC\n                    <jats:sub>PRS<\/jats:sub>\n                    =0\u00b7564 [0\u00b7556-0\u00b7573] vs AUC\n                    <jats:sub>Gail<\/jats:sub>\n                    =0\u00b7506 [0\u00b7497-0\u00b7514]). PRS\n                    <jats:sub>binary<\/jats:sub>\n                    and GAIL\n                    <jats:sub>binary<\/jats:sub>\n                    identified more high-risk European than Asia individuals. High-risk proportions were higher among BrCa (16-26%) and DCIS (20-33%) compared to controls (9-15%) among young Europeans and all Asians. Fewer than 7% of BrCa, 10% of DCIS, and 3% of controls were classified as high-risk by multiple risk classifiers. Overlap between PRS\n                    <jats:sub>binary<\/jats:sub>\n                    and PTV\n                    <jats:sub>binary<\/jats:sub>\n                    was minimal (&lt;0\u00b765% Europeans, &lt;0\u00b715% Asians) compared to the proportion at high risk using PTV\n                    <jats:sub>binary<\/jats:sub>\n                    alone (Europeans: 4\u00b76%, Asians: 4\u00b74%) and PRS\n                    <jats:sub>binary<\/jats:sub>\n                    alone (Europeans: 13\u00b79%, Asians: 8\u00b75%). PRS\n                    <jats:sub>binary<\/jats:sub>\n                    and FH\n                    <jats:sub>binary<\/jats:sub>\n                    uniquely identified 5-6% and 9-11% of young BrCa, respectively.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Interpretation<\/jats:title>\n                  <jats:p>\n                    The incomplete overlap between high-risk individuals identified by PRS\n                    <jats:sub>binary<\/jats:sub>\n                    , GAIL\n                    <jats:sub>binary<\/jats:sub>\n                    , FH\n                    <jats:sub>binary,<\/jats:sub>\n                    and PTV\n                    <jats:sub>binary<\/jats:sub>\n                    highlights the need for a comprehensive approach to breast cancer risk prediction.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>SIGNIFICANCE<\/jats:title>\n                  <jats:p>This study shows that different ways of predicting breast cancer risk do not always flag the same people, suggesting that combining multiple risk factors could improve early detection and screening.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.02.27.25323002","type":"posted-content","created":{"date-parts":[[2025,3,3]],"date-time":"2025-03-03T19:30:13Z","timestamp":1741030213000},"source":"Crossref","is-referenced-by-count":0,"title":["Overlap of high-risk individuals across family history, genetic &amp; non-genetic breast cancer risk models: Analysis of 180,398 women from European &amp; Asian ancestries"],"prefix":"10.64898","author":[{"given":"Peh Joo","family":"Ho","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine Kim Yan","family":"Loo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meng Huang","family":"Goh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mustapha","family":"Abubakar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas U.","family":"Ahearn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irene L.","family":"Andrulis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalia N.","family":"Antonenkova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristan J.","family":"Aronson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annelie","family":"Augustinsson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabine","family":"Behrens","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clara","family":"Bodelon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalia V.","family":"Bogdanova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manjeet K.","family":"Bolla","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristen","family":"Brantley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hermann","family":"Brenner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helen","family":"Byers","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicola J.","family":"Camp","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jose E.","family":"Castelao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melissa H.","family":"Cessna","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jenny","family":"Chang-Claude","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen J.","family":"Chanock","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georgia","family":"Chenevix-Trench","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji-Yeob","family":"Choi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah V.","family":"Colonna","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kamila","family":"Czene","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary B.","family":"Daly","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francoise","family":"Derouane","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thilo","family":"D\u00f6rk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. 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