{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T02:35:11Z","timestamp":1793414111386,"version":"4.5.0"},"reference-count":15,"publisher":"American Medical Association (AMA)","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Oncol"],"published-print":{"date-parts":[[2026,8,1]]},"abstract":"<jats:sec>\n                    <jats:title>Importance<\/jats:title>\n                    <jats:p>Risk-based breast cancer screening has emerged as a viable alternative to annual mammography. To guide implementation, knowledge is needed on the contribution of testing for pathogenic variants (PVs) beyond clinical risk factors and common genetic variants for population-based risk stratification.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To evaluate how many PV carriers in a risk-based breast cancer screening trial would have been recommended for high-risk screening based on clinical risk or clinical plus polygenic risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design, Setting, and Participants<\/jats:title>\n                    <jats:p>This cohort study used retrospective data from the WISDOM Study, a national clinical trial of risk-based vs annual breast cancer screening, to compare screening assignments informed by PV status vs those based on a clinical risk model alone or a clinical risk model combined with a polygenic risk score. WISDOM participants aged 40 to 74 years who tested positive for a PV as part of risk-based screening were included. Data were collected from September 2016 to February 2023, with follow-up to September 2025. Data were analyzed from January to May 2026.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Main Outcomes and Measures<\/jats:title>\n                    <jats:p>Concordance between actual (considering participants\u2019 PV status) and hypothetical screening assignments based on a clinical (Breast Cancer Surveillance Consortium) risk model or a clinical model plus polygenic risk score.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of 712 included women with a PV, the median (IQR) age was 53 (46-62) years. A total of 232 PVs (33%) were high penetrance, 278 (39%) were moderate penetrance, and 202 (28%) were\n                      <jats:italic>CHEK2<\/jats:italic>\n                      low penetrance. There was little overlap between actual screening assignments based on PV status and hypothetical assignments based on a clinical model plus polygenic risk score. Among high-penetrance PV carriers (a group recommended high-risk screening with magnetic resonance imaging alternating with mammography every 6 months), 2 of 232 (0.9%) would have received the same screening assignment based on clinical plus polygenic risk. Overall, 178 of 279 PV carriers aged 40 to 49 years (63.8%) would have otherwise been recommended to defer screening until age 50 years based on clinical plus polygenic risk, whereas 385 of 433 carriers aged 50 to 74 years (88.9%) would have been recommended biennial mammography. Results were similar when comparing assignments based on a clinical model alone.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Relevance<\/jats:title>\n                    <jats:p>In this cohort study, most participants with PVs in breast cancer genes would not have been recommended for high-risk screening based on their clinical or clinical plus polygenic risk. PV testing therefore may identify different subsets of high-risk women than clinical risk factors and polygenic risk scores. These findings highlight the importance of population-based PV testing in risk-based screening.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>\n                      ClinicalTrials.gov Identifier:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/study\/NCT02620852\">NCT02620852<\/jats:ext-link>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1001\/jamaoncol.2026.2091","type":"journal-article","created":{"date-parts":[[2026,5,31]],"date-time":"2026-05-31T15:30:14Z","timestamp":1780241414000},"page":"875","source":"Crossref","is-referenced-by-count":1,"title":["Impact of Population-Based Pathogenic Variant Testing on Risk-Based Breast Screening Recommendations"],"prefix":"10.1001","volume":"12","author":[{"given":"Yiwey","family":"Shieh","sequence":"first","affiliation":[{"name":"Department of Population Health Sciences, Weill Cornell Medicine, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel S.","family":"Heise","sequence":"additional","affiliation":[{"name":"Department of Population Health Sciences, Weill Cornell Medicine, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Madlensky","sequence":"additional","affiliation":[{"name":"Division of Genomics and Precision Medicine, Department of Medicine, University of California, San Diego, La Jolla"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leah P.","family":"Sabacan","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of California, San Francisco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene 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