{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T12:40:34Z","timestamp":1760532034522,"version":"build-2065373602"},"reference-count":38,"publisher":"BMJ","issue":"7","license":[{"start":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T00:00:00Z","timestamp":1744243200000},"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":["PPRPGM-Nov20\\100002"],"award-info":[{"award-number":["PPRPGM-Nov20\\100002"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIHR Cambridge Biomedical Research Centre","award":["NIHR203312"],"award-info":[{"award-number":["NIHR203312"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2025,3,22]]},"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>The management of women with germline pathogenic variants (GPVs) in breast (BC) and ovarian cancer (OC) susceptibility genes is focused on surveillance and risk-reducing surgery\/medication. Most women are assigned an average range of risk and treated accordingly, but it is possible to personalise this. Here, we explore the economic impact of risk personalisation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Method<\/jats:title>\n                  <jats:p>We compared two strategies for risk stratification for female participants: conventional risk assessment (CRA), which only involves information from genetic testing and personalised risk assessment (PRA), using genetic and non-genetic risk modifiers. Three different versions of PRA were compared, which were combinations of polygenic risk score and questionnaire-based factors. A patient-level Markov model was designed to estimate the overall National Health Service cost and quality-adjusted life years (QALYs) after risk assessment. Results were given for 20 different groups of women based on their GPV status and family history.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Across the 20 scenarios, the results showed that PRA was cost-effective compared with CRA using a \u00a320 000 per QALY threshold in women with a GPV in <jats:italic>PALB2<\/jats:italic> who have OC or BC+OC family history, and women with a GPV in <jats:italic>ATM<\/jats:italic>, <jats:italic>CHEK2<\/jats:italic>, <jats:italic>RAD51C<\/jats:italic> or <jats:italic>RAD51D<\/jats:italic>. For women with a GPV in <jats:italic>BRCA1<\/jats:italic> or <jats:italic>BRCA2<\/jats:italic>, women with no pathogenic variant and women with a GPV in <jats:italic>PALB2<\/jats:italic> who have unknown family history or BC family history, CRA was more cost-effective. PRA was cost-effective compared with CRA in specific situations predominantly associated with moderate-risk BC GPVs (<jats:italic>RAD51C<\/jats:italic>\/<jats:italic>RAD51D<\/jats:italic>\/<jats:italic>CHEK2<\/jats:italic>\/<jats:italic>ATM<\/jats:italic>), while CRA was cost-effective compared with PRA predominantly with high-risk BC GPVs (<jats:italic>BRCA1<\/jats:italic>\/<jats:italic>BRCA2<\/jats:italic>\/<jats:italic>PALB2<\/jats:italic>).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>PRA was cost-effective in specific situations compared with CRA in the UK for assessment of women with or without GPVs in BC and OC susceptibility genes.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jmg-2024-109948","type":"journal-article","created":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T13:20:18Z","timestamp":1744291218000},"page":"450-456","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Economic evaluation of personalised versus conventional risk assessment for women who have undergone testing for hereditary breast and ovarian cancer genes: a modelling study"],"prefix":"10.1136","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9712-4688","authenticated-orcid":false,"given":"Qin","family":"Xi","sequence":"first","affiliation":[{"name":"Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nichola","family":"Fennell","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, University of Cambridge, Cambridge, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephanie","family":"Archer","sequence":"additional","affiliation":[{"name":"Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc","family":"Tischkowitz","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, University of Cambridge, Cambridge, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9223-3116","authenticated-orcid":false,"given":"Antonis C","family":"Antoniou","sequence":"additional","affiliation":[{"name":"Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen","family":"Morris","sequence":"additional","affiliation":[{"name":"Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2025,4,10]]},"reference":[{"key":"2025101505050572000_62.7.450.1","unstructured":"World Health Organization (WHO) . 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