{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:58:44Z","timestamp":1785437924720,"version":"3.56.0"},"reference-count":56,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T00:00:00Z","timestamp":1777939200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Government of Canada through Genome Canada","award":["13529"],"award-info":[{"award-number":["13529"]}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["155865"],"award-info":[{"award-number":["155865"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"award":["155865"],"award-info":[{"award-number":["155865"]}],"id":[{"id":"https:\/\/ror.org\/01gavpb45","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Minist\u00e8re de l\u2019\u00c9conomie et de l\u2019Innovation du Qu\u00e9bec through G\u00e9nome Qu\u00e9bec"},{"DOI":"10.13039\/100016328","name":"Quebec Breast Cancer Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100016328","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/00dfyw498","id-type":"ROR","asserted-by":"publisher"}]},{"name":"CHU de Qu\u00e9bec Foundation"},{"name":"CHU de Qu\u00e9bec-Universit\u00e9 Laval Research Center and the Ontario Research Fund"},{"DOI":"10.13039\/501100018956","name":"NIHR Cambridge Biomedical Research Centre","doi-asserted-by":"publisher","award":["NIHR203312"],"award-info":[{"award-number":["NIHR203312"]}],"id":[{"id":"10.13039\/501100018956","id-type":"DOI","asserted-by":"publisher"}]},{"award":["NIHR203312"],"award-info":[{"award-number":["NIHR203312"]}],"id":[{"id":"https:\/\/ror.org\/05m8dr349","id-type":"ROR","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\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["SEBCD3-2024\/100001"],"award-info":[{"award-number":["SEBCD3-2024\/100001"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["EDDPMA-May23\/100008"],"award-info":[{"award-number":["EDDPMA-May23\/100008"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"award":["PPRPGM-Nov20\\100002"],"award-info":[{"award-number":["PPRPGM-Nov20\\100002"]}],"id":[{"id":"https:\/\/ror.org\/054225q67","id-type":"ROR","asserted-by":"publisher"}]},{"award":["SEBCD3-2024\/100001"],"award-info":[{"award-number":["SEBCD3-2024\/100001"]}],"id":[{"id":"https:\/\/ror.org\/054225q67","id-type":"ROR","asserted-by":"publisher"}]},{"award":["EDDPMA-May23\/100008"],"award-info":[{"award-number":["EDDPMA-May23\/100008"]}],"id":[{"id":"https:\/\/ror.org\/054225q67","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Risk-based breast cancer (BC) screening can provide tailored recommendations based on individual risk. We aimed to identify key predictors for BC risk stratification to inform implementation in screening programs. Methods: We estimated 10-year BC risks using BOADICEA v.6 (CanRisk) in 3753 women aged 40\u201370 with no cancer history from the PERSPECTIVE I&amp;I cohort. The primary endpoint was risk reclassification, assessed as the proportion of women whose assigned 10-year risk category changed when using different risk factor combinations against a full multifactorial model including questionnaire-based risk factors (QRFs), polygenic score (PGS), mammographic density (MD), and pedigree-structured first- and second-degree family history (FH) of breast, ovarian, pancreatic and prostate cancer, including both affected and unaffected relatives. Relative risk thresholds were set as &lt;1.5 (average), 1.5\u20132.7 (higher-than-average), and \u22652.7 (high), equivalent to the remaining lifetime risk categories of &lt;15%, 15\u201325% and \u226525% for women aged 30 (the anchor) to age 80. We quantified individual-level reclassification flows by direction and magnitude. Results: Excluding PGS from risk calculations led to the highest overall reclassification. Using only the BC status in first- and second-degree relatives produced comparable risk classification to that of the full FH data that included breast, ovarian, prostate and pancreatic cancer (reclassification = 0.5%). However, collecting only affected relatives led to overestimation of risk. Excluding either PGS, MD or FH resulted in a greater proportion of reclassification among younger women. Adding the PGS to risk factors already collected in provincial screening programs reduced reclassification from 23% to ~13%. Conclusions: PGS, MD, QRFs and FH of BC in affected and unaffected first- and second-degree relatives are key for refining risk stratification. These findings provide real-world evidence on how incorporating different sets of risk factors, both those routinely collected in screening programs and those requiring additional data collection, affect individual-level risk classification amongst a population-based cohort, and how the impacts differ across age groups. While risk classification reflects model-based changes in estimated risk categories rather than direct evidence of mis-screening or clinical outcomes, comparison with the current eligibility criteria used to identify women at higher-than-average risk highlights the potential clinical value of a multifactorial risk assessment approach in ensuring more appropriate screening strategies.<\/jats:p>","DOI":"10.3390\/cancers18091482","type":"journal-article","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T13:23:37Z","timestamp":1777987417000},"page":"1482","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Contribution of Risk Factors, Including Polygenic Score, to the Multifactorial Risk Assessment for the Implementation of Personalized Breast Cancer Screening: Insights from the PERSPECTIVE: Integration and Implementation Project"],"prefix":"10.3390","volume":"18","author":[{"given":"Xin","family":"Yang","sequence":"first","affiliation":[{"name":"Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, School of Clinical Medicine, University of Cambridge, Cambridge CB1 8RN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliet A.","family":"Usher-Smith","sequence":"additional","affiliation":[{"name":"Primary Care Unit, Department of Public Health and Primary Care, School of Clinical Medicine, University of Cambridge, Cambridge CB1 8RN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina M.","family":"Blackmore","sequence":"additional","affiliation":[{"name":"Ontario Health, Toronto, ON M5G 2L3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7574-4256","authenticated-orcid":false,"given":"Jennifer D.","family":"Brooks","sequence":"additional","affiliation":[{"name":"Dalla Lana School of Public Health, University of Toronto, Toronto, ON M5S 1A1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen A.","family":"Bell","sequence":"additional","affiliation":[{"name":"Ontario Health, Toronto, ON M5G 2L3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1508-3091","authenticated-orcid":false,"given":"Tim","family":"Carver","sequence":"additional","affiliation":[{"name":"Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, School of Clinical Medicine, University of Cambridge, Cambridge CB1 8RN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Chang","sequence":"additional","affiliation":[{"name":"Ontario Health, Toronto, ON M5G 2L3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3556-4677","authenticated-orcid":false,"given":"Jocelyne","family":"Chiquette","sequence":"additional","affiliation":[{"name":"CHU de Qu\u00e9bec-Universit\u00e9 Laval Research Center, Quebec City, QC G1V 4G2, Canada"},{"name":"Department of Family Medicine and Emergency Medicine, Faculty of Medicine, Universit\u00e9 Laval, Quebec City, QC G1V 0A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas F.","family":"Easton","sequence":"additional","affiliation":[{"name":"Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, School of Clinical Medicine, University of Cambridge, Cambridge CB1 8RN, UK"},{"name":"Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge CB1 8RN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8037-9556","authenticated-orcid":false,"given":"Andrea","family":"Eisen","sequence":"additional","affiliation":[{"name":"Ontario Health, Toronto, ON M5G 2L3, Canada"},{"name":"Sunnybrook Health Science Centre, Toronto, ON M4N 3M5, Canada"},{"name":"Department of Oncology, McMaster University, Hamilton, ON L8V 5C2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Eloy","sequence":"additional","affiliation":[{"name":"Programme Qu\u00e9b\u00e9cois de Canc\u00e9rologie, Minist\u00e8re de la Sant\u00e9 et des Services Sociaux, Quebec City, QC G1S 2M1, Canada"},{"name":"Centre Int\u00e9gr\u00e9 de Sant\u00e9 et de Services Sociaux de Lanaudi\u00e8re, Centre hospitalier de Lanaudi\u00e8re, Saint-Charles Borrom\u00e9e, QC J6E 6J2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9314-657X","authenticated-orcid":false,"given":"Samantha","family":"Fienberg","sequence":"additional","affiliation":[{"name":"Ontario Health, Toronto, ON M5G 2L3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yann","family":"Joly","sequence":"additional","affiliation":[{"name":"Centre of Genomics and Policy, McGill University, Montreal, QC H3A 0G1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2147-8674","authenticated-orcid":false,"given":"Raymond H.","family":"Kim","sequence":"additional","affiliation":[{"name":"Ontario Health, Toronto, ON M5G 2L3, Canada"},{"name":"Princess Margaret Cancer Centre, Toronto, ON M5G 2M9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7004-2722","authenticated-orcid":false,"given":"Bartha M.","family":"Knoppers","sequence":"additional","affiliation":[{"name":"Centre of Genomics and Policy, McGill University, Montreal, QC H3A 0G1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2598-7094","authenticated-orcid":false,"given":"Laurence","family":"Lambert-C\u00f4t\u00e9","sequence":"additional","affiliation":[{"name":"CHU de Qu\u00e9bec-Universit\u00e9 Laval Research Center, Quebec City, QC G1V 4G2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7832-0413","authenticated-orcid":false,"given":"Hermann","family":"Nabi","sequence":"additional","affiliation":[{"name":"CHU de Qu\u00e9bec-Universit\u00e9 Laval Research Center, Quebec City, QC G1V 4G2, Canada"},{"name":"Department of Social and Preventive Medicine, Faculty of Medicine, Universit\u00e9 Laval, Quebec City, QC G1V 0A6, Canada"},{"name":"Universit\u00e9 Laval Cancer Research Center, Quebec City, QC G1R 3S3, 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Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1941-955X","authenticated-orcid":false,"given":"Michael","family":"Wolfson","sequence":"additional","affiliation":[{"name":"School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON K1G 5Z3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3207-8211","authenticated-orcid":false,"given":"Michel","family":"Dorval","sequence":"additional","affiliation":[{"name":"CHU de Qu\u00e9bec-Universit\u00e9 Laval Research Center, Quebec City, QC G1V 4G2, Canada"},{"name":"Universit\u00e9 Laval Cancer Research Center, Quebec City, QC G1R 3S3, Canada"},{"name":"Faculty of Pharmacy, Universit\u00e9 Laval, Quebec City, QC G1V 0A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna M.","family":"Chiarelli","sequence":"additional","affiliation":[{"name":"Dalla Lana School of Public Health, University of Toronto, Toronto, ON M5S 1A1, Canada"}],"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, School of Clinical Medicine, University of Cambridge, Cambridge CB1 8RN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6906-3390","authenticated-orcid":false,"given":"Jacques","family":"Simard","sequence":"additional","affiliation":[{"name":"CHU de Qu\u00e9bec-Universit\u00e9 Laval Research Center, Quebec City, QC G1V 4G2, Canada"},{"name":"Universit\u00e9 Laval Cancer Research Center, Quebec City, QC G1R 3S3, Canada"},{"name":"Department of Molecular Medicine, Faculty of Medicine, Universit\u00e9 Laval, Quebec City, QC G1V 4G2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"E1441","DOI":"10.1503\/cmaj.180463","article-title":"Recommendations on screening for breast cancer in women aged 40\u201374 years who are not at increased risk for breast cancer","volume":"190","author":"Klarenbach","year":"2018","journal-title":"CMAJ"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"E1432","DOI":"10.1503\/cmaj.181538","article-title":"Wise guidance and its challenges: The new Canadian recommendations on breast cancer screening","volume":"190","author":"Korenstein","year":"2018","journal-title":"CMAJ"},{"key":"ref_3","unstructured":"Cancer Care Ontario (2025, April 15). 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