{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T15:55:18Z","timestamp":1781711718145,"version":"3.54.5"},"reference-count":39,"publisher":"American Medical Association (AMA)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n Validating polygenic risk scores (PRSs) as a breast cancer (BC) risk stratification tool in high-risk clinical settings is essential for potential clinical implementation.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To evaluate the performance of African-ancestry PRSs for overall BC and triple-negative BC (TNBC) in an independent African American cohort at elevated familial risk.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This case-control study was conducted among women with self-reported African ancestry in a clinical hereditary cancer genetic testing setting who had negative results for pathogenic or likely pathogenic variants in known BC-associated genes between 2016 to 2024. Analyses were performed from September 2025 to April 2026.<\/jats:p>\n <\/jats:sec>\n \n Exposure<\/jats:title>\n Six African-ancestry PRSs and a European-ancestry PRS (PRS-313).<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n Performance of the PRSs was measured with covariate-adjusted area under the receiver operating characteristic curve (AUC) and adjusted odds ratio (OR) per 1 SD from logistic regression adjusting for age, top 10 genetic principal components, and family history.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n This study included 31\u202f522 women (mean [SD] age, 47.1 [13.3] years): 12\u202f067 women with BC (2311 with TNBC) and 19\u202f455 women unaffected by BC. Women unaffected by BC were younger at testing than women with BC at diagnosis (mean [SD] age, 42.1 [11.7] years vs 55.2 [11.8] years) and were more likely to report a first- and second-degree family history of BC than women with BC (14\u202f524 women [74.7%] vs 6483 women [53.7%]). For overall BC, PRS-313 showed an AUC of 0.567 (95% CI, 0.560-0.574) and an OR of 1.28 (95% CI, 1.25-1.31) per 1 SD of individuals unaffected by BC. In comparison, the African overall BC models 1 (2\u202f324\u202f063-variant model) and 2 (175\u202f173-variant model) performed better, with AUCs of 0.588 (95% CI, 0.580-0.595) and 0.584 (95% CI, 0.576-0.591) and ORs of 1.39 (95% CI, 1.35-1.43) and 1.37 (95% CI, 1.34-1.41) per 1 SD of individuals unaffected by BC, respectively. Importantly, for TNBC, one 162-variant PRS consistently outperformed all other models, with an AUC of 0.609 (95% CI, 0.596-0.622) and an OR of 1.47 (95% CI, 1.40-1.55) per 1 SD of individuals unaffected by BC.<\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n In this clinically ascertained case-control study of self-reported Black or African American women, the PRSs demonstrated good performance among women with a strong family history of BC, reflecting populations in whom early PRS testing is most relevant. The high accuracy of the 162-variant TNBC PRS supported its potential as a cost-effective risk assessment tool to promote equitable care.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2026.19285","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T15:30:46Z","timestamp":1781710246000},"page":"e2619285","source":"Crossref","is-referenced-by-count":0,"title":["Polygenic Risk Scores for Breast Cancer Among African American Women With High Risk"],"prefix":"10.1001","volume":"9","author":[{"given":"Yijia","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Public Health Sciences, University of Chicago, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Simmons","sequence":"additional","affiliation":[{"name":"Myriad Genetics, Inc, Salt Lake City, Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James L.","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Public Health Sciences, University of Chicago, Chicago, Illinois"},{"name":"Interdisciplinary Scientist Training Program, University of Chicago, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armaan","family":"Jamal","sequence":"additional","affiliation":[{"name":"Department of Public Health Sciences, University of Chicago, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Achille V. 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