{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T18:56:00Z","timestamp":1787943360723,"version":"build-2784847793"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2021,3,3]],"date-time":"2021-03-03T00:00:00Z","timestamp":1614729600000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Australian National Health and Medical Research Council"},{"DOI":"10.13039\/501100000951","name":"Cancer Council Victoria","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000951","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Australian NHMRC","award":["209057"],"award-info":[{"award-number":["209057"]}]},{"name":"Australian NHMRC","award":["396414"],"award-info":[{"award-number":["396414"]}]},{"name":"Australian NHMRC","award":["1074383"],"award-info":[{"award-number":["1074383"]}]},{"name":"Cancer Council Victoria since 1995"},{"DOI":"10.13039\/501100001026","name":"National Breast Cancer Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001026","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research - UK","doi-asserted-by":"crossref","award":["C12292\/A20861"],"award-info":[{"award-number":["C12292\/A20861"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,5,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm and the International Breast Cancer Intervention Study breast cancer risk models are used to provide advice on screening intervals and chemoprevention. We evaluated the performance of these models, which now incorporate polygenic risk scores (PRSs), using a prospective cohort study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We used a case-cohort design, involving women in the Melbourne Collaborative Cohort Study aged 50-75\u2009years when surveyed in 2003-2007, of whom 408 had a first primary breast cancer diagnosed within 10\u2009years (cases), and 2783 were from the subcohort. Ten-year risks were calculated based on lifestyle factors, family history data, and a 313-variant PRS. Discrimination was assessed using a C-statistic compared with 0.50 and calibration using the ratio of expected to observed number of cases (E\/O).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>When the PRS was added to models with lifestyle factors and family history, the C-statistic (95% confidence interval [CI]) increased from 0.57 (0.54 to 0.60) to 0.62 (0.60 to 0.65) using IBIS and from 0.56 (0.53 to 0.59) to 0.62 (0.59 to 0.64) using BOADICEA. IBIS underpredicted risk (E\/O\u2009=\u20090.62, 95% CI = 0.48 to 0.80) for women in the lowest risk category (&amp;lt;1.7%) and overpredicted risk (E\/O\u2009=\u20091.40, 95% CI = 1.18 to 1.67) in the highest risk category (\u22655%), using the Hosmer-Lemeshow test for calibration in quantiles of risk and a 2-sided P value less than\u2009\u2009.001. BOADICEA underpredicted risk (E\/O\u2009=\u20090.82, 95% CI = 0.67 to 0.99) in the second highest risk category (3.4%-5%); the Hosmer-Lemeshow test and a 2-sided P value\u2009was equal to .02.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Although the inclusion of a 313 genetic variant PRS doubles discriminatory accuracy (relative to reference 0.50), models with and without this PRS have relatively modest discrimination and might require recalibration before their clinical and wider use are promoted.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jncics\/pkab021","type":"journal-article","created":{"date-parts":[[2021,2,25]],"date-time":"2021-02-25T12:45:56Z","timestamp":1614257156000},"source":"Crossref","is-referenced-by-count":38,"title":["Prospective Evaluation of the Addition of Polygenic Risk Scores to Breast Cancer Risk 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University of Melbourne, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graham G","family":"Giles","sequence":"additional","affiliation":[{"name":"Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia"},{"name":"Centre for Epidemiology and Biostatistics, University of Melbourne, Melbourne, Victoria, Australia"},{"name":"Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6313-9005","authenticated-orcid":false,"given":"Melissa C","family":"Southey","sequence":"additional","affiliation":[{"name":"Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia"},{"name":"Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Melbourne, Victoria, Australia"},{"name":"Department of Clinical Pathology, The University of Melbourne, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonis C","family":"Antoniou","sequence":"additional","affiliation":[{"name":"Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, Strangeways Research Laboratory, University of Cambridge, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0677-0252","authenticated-orcid":false,"given":"Andrew","family":"Lee","sequence":"additional","affiliation":[{"name":"Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, Strangeways Research Laboratory, University of Cambridge, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7840-4051","authenticated-orcid":false,"given":"Shuai","family":"Li","sequence":"additional","affiliation":[{"name":"Centre for Epidemiology and Biostatistics, 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