{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T19:11:51Z","timestamp":1792696311006,"version":"4.5.0"},"reference-count":26,"publisher":"BMJ","issue":"8","license":[{"start":{"date-parts":[[2024,6,4]],"date-time":"2024-06-04T00:00:00Z","timestamp":1717459200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C12292\/A20861"],"award-info":[{"award-number":["C12292\/A20861"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["PPRPGM-Nov20\\100002"],"award-info":[{"award-number":["PPRPGM-Nov20\\100002"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018956","name":"NIHR Cambridge BRC","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100018956","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2024,5,12]]},"published-print":{"date-parts":[[2024,8]]},"abstract":"\n Background<\/jats:title>\n \n No validation has been conducted for the BOADICEA multifactorial breast cancer risk prediction model specifically in\n BRCA1\/2<\/jats:italic>\n pathogenic variant (PV) carriers to date. Here, we evaluated the performance of BOADICEA in predicting 5-year breast cancer risks in a prospective cohort of\n BRCA1\/2<\/jats:italic>\n PV carriers ascertained through clinical genetic centres.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We evaluated the model calibration and discriminatory ability in the prospective TRANsIBCCS cohort study comprising 1614\n BRCA1<\/jats:italic>\n and 1365\n BRCA2<\/jats:italic>\n PV carriers (209 incident cases). Study participants had lifestyle, reproductive, hormonal, anthropometric risk factor information, a polygenic risk score based on 313 SNPs and family history information.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The full multifactorial model considering family history together with all other risk factors was well calibrated overall (E\/O=1.07, 95% CI: 0.92 to 1.24) and in quintiles of predicted risk. Discrimination was maximised when all risk factors were considered (Harrell\u2019s C-index=0.70, 95% CI: 0.67 to 0.74; area under the curve=0.79, 95% CI: 0.76 to 0.82). The model performance was similar when evaluated separately in\n BRCA1<\/jats:italic>\n or\n BRCA2<\/jats:italic>\n PV carriers. The full model identified 5.8%, 12.9% and 24.0% of\n BRCA1\/2<\/jats:italic>\n PV carriers with 5-year breast cancer risks of <1.65%, <3%\u2009and <5%, respectively, risk thresholds commonly used for different management and risk-reduction options.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n BOADICEA may be used to aid personalised cancer risk management and decision-making for\n BRCA1<\/jats:italic>\n and\n BRCA2<\/jats:italic>\n PV carriers. It is implemented in the free-access CanRisk tool (\n https:\/\/www.canrisk.org\/<\/jats:ext-link>\n ).\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1136\/jmg-2024-109943","type":"journal-article","created":{"date-parts":[[2024,6,4]],"date-time":"2024-06-04T16:22:29Z","timestamp":1717518149000},"page":"803-809","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":17,"title":["Validation of the BOADICEA model in a prospective cohort of\n BRCA1\/2<\/i>\n pathogenic variant carriers"],"prefix":"10.1136","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0037-3790","authenticated-orcid":false,"given":"Xin","family":"Yang","sequence":"first","affiliation":[{"name":"Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thea M","family":"Mooij","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Goska","family":"Leslie","sequence":"additional","affiliation":[{"name":"Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0577-1571","authenticated-orcid":false,"given":"Lorenzo","family":"Ficorella","sequence":"additional","affiliation":[{"name":"Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine","family":"Andrieu","sequence":"additional","affiliation":[{"name":"INSERM U900, Paris, France"},{"name":"Institut Curie, Paris, France"},{"name":"Mines ParisTech, Fontainebleau, France"},{"name":"PSL Research University, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Kast","sequence":"additional","affiliation":[{"name":"Center for Hereditary Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Medical Faculty, University Hospital Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian F.","family":"Singer","sequence":"additional","affiliation":[{"name":"Department of OB\/GYN and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Jakubowska","sequence":"additional","affiliation":[{"name":"Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland"},{"name":"Independent Laboratory of Molecular Biology and Genetic Diagnostics, Pomeranian Medical University, Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla H","family":"van Gils","sequence":"additional","affiliation":[{"name":"Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yen Y","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of OB\/GYN and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Engel","sequence":"additional","affiliation":[{"name":"Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muriel A","family":"Adank","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christi J","family":"van Asperen","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margreet G E M","family":"Ausems","sequence":"additional","affiliation":[{"name":"Devision Laboratories, Pharmacy and Biomedical Genetics, Department of Genetics, University Medical Centre Utrecht, Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascaline","family":"Berthet","sequence":"additional","affiliation":[{"name":"Oncog\u00e9n\u00e9tique D\u00e9partement de Biopathologie, Centre Fran\u00e7ois Baclesse, Caen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"EMBRACE collaborators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margriet J","family":"Collee","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jackie A","family":"Cook","sequence":"additional","affiliation":[{"name":"Sheffield Clinical Genetics Service, Scheffield Children's Hospital, Sheffield, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline","family":"Eason","sequence":"additional","affiliation":[{"name":"Nottingham Clinical Genetics Service, Nottingham University Hospitals NHS Trust, Nottingham, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin Y van","family":"Spaendonck-Zwarts","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Amsterdam University Medical Centres, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. Gareth","family":"Evans","sequence":"additional","affiliation":[{"name":"The Prevent Breast Cancer Research Unit, The Nightingale Centre, Manchester University NHS Foundation Trust, Manchester, UK"},{"name":"Genomic Medicine, Division of Evolution and Genomic Sciences, The University of Manchester, St Mary\u2019s Hospital, Manchester University NHS Foundation Trust, Manchester, UK"},{"name":"Manchester Breast Centre, Oglesby Cancer Research Centre, The Christie, University of Manchester, Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Encarna B","family":"G\u00f3mez Garc\u00eda","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Maastricht University, Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3303-8713","authenticated-orcid":false,"given":"Helen","family":"Hanson","sequence":"additional","affiliation":[{"name":"South West Thames Regional 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UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Lasset","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Claude Bernard Lyon 1, Villeurbanne, France"},{"name":"CNRS UMR 5558, Lyon, France"},{"name":"Centre L\u00e9on B\u00e9rard, Unit\u00e9 de Pr\u00e9vention et Epid\u00e9miologie G\u00e9n\u00e9tique, Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabienne","family":"Lesueur","sequence":"additional","affiliation":[{"name":"INSERM U900, Paris, France"},{"name":"Institut Curie, Paris, France"},{"name":"Mines ParisTech, Fontainebleau, France"},{"name":"PSL Research University, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Musgrave","sequence":"additional","affiliation":[{"name":"Yorkshire Regional Genetics Service, Leeds Teaching Hospitals NHS Trust, Leeds, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Nambot","sequence":"additional","affiliation":[{"name":"Centre de G\u00e9n\u00e9tique et Centre de R\u00e9f\u00e9rence Anomalies du D\u00e9veloppement et Syndromes Malformatifs, CHU de Dijon, H\u00f4pital d\u2019Enfants, Dijon, France"},{"name":"Centre de Lutte contre le Cancer Georges Fran\u00e7ois Leclerc, Dijon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Nogu\u00e8s","sequence":"additional","affiliation":[{"name":"D\u00e9partement d\u2019Anticipation et de Suivi des Cancers, Oncog\u00e9n\u00e9tique Clinique, Institut Paoli Calmettes, Marseille, France"},{"name":"Aix Marseille Univ, INSERM, IRD, SESSTIM, Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan C","family":"Oosterwijk","sequence":"additional","affiliation":[{"name":"Department of Genetics, University of Groningen, University Medical Center, Groningen, The 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