{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T05:21:53Z","timestamp":1783401713520,"version":"3.54.6"},"reference-count":12,"publisher":"BMJ","issue":"9","license":[{"start":{"date-parts":[[2024,4,12]],"date-time":"2024-04-12T00:00:00Z","timestamp":1712880000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014653","name":"Manchester Biomedical Research Centre","doi-asserted-by":"publisher","award":["IS-BRC-1215-20007"],"award-info":[{"award-number":["IS-BRC-1215-20007"]}],"id":[{"id":"10.13039\/100014653","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C19941\/A27859"],"award-info":[{"award-number":["C19941\/A27859"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2024,3,23]]},"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Male breast cancer (MBC) affects around 1 in 1000 men and is known to have a higher underlying component of high and moderate risk gene pathogenic variants (PVs) than female breast cancer, particularly in <jats:italic>BRCA2<\/jats:italic>. However, most studies only report overall detection rates without assessing detailed family history.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We reviewed germline testing in 204 families including at least one MBC for <jats:italic>BRCA1<\/jats:italic>, <jats:italic>BRCA2<\/jats:italic>, <jats:italic>CHEK2<\/jats:italic> c.1100DelC and an extended panel in 93 of these families. Individuals had MBC (n=118), female breast cancer (FBC)(n=80), ovarian cancer (n=3) or prostate cancer-(n=3). Prior probability of having a <jats:italic>BRCA1\/2<\/jats:italic> PV was assessed using the Manchester Scoring System (MSS).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In the 204 families, <jats:italic>BRCA2<\/jats:italic> was the major contributor, with 51 (25%) having PVs, followed by <jats:italic>BRCA1<\/jats:italic> and <jats:italic>CHEK2,<\/jats:italic> with five each (2.45%) but no additional PVs identified, including in families with high genetic likelihood on MSS. Detection rates were 85.7% (12\/14) in MSS \u226540 and 65.5% with MSS 30\u201339 but only 12.8% (6\/47) for sporadic breast cancer. PV rates were low and divided equally between <jats:italic>BRCA1\/2<\/jats:italic> and <jats:italic>CHEK2.<\/jats:italic>\n                  <\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>As expected, <jats:italic>BRCA2<\/jats:italic> PVs predominate in MBC families with rates 10-fold those in <jats:italic>CHEK2<\/jats:italic> and <jats:italic>BRCA1<\/jats:italic>. The MSS is an effective tool in assessing the likelihood of <jats:italic>BRCA1\/2<\/jats:italic> PVs.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jmg-2023-109826","type":"journal-article","created":{"date-parts":[[2024,4,12]],"date-time":"2024-04-12T13:20:29Z","timestamp":1712928029000},"page":"853-855","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":7,"title":["Pathogenic variant detection rate varies considerably in male breast cancer families and sporadic cases: minimal additional contribution beyond <i>BRCA2, BRCA1<\/i> and <i>CHEK2<\/i>"],"prefix":"10.1136","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8482-5784","authenticated-orcid":false,"given":"D Gareth","family":"Evans","sequence":"first","affiliation":[{"name":"Genomic Medicine, MAHSC, Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9360-8194","authenticated-orcid":false,"given":"George J","family":"Burghel","sequence":"additional","affiliation":[{"name":"Genomic Diagnostic Laboratory, Manchester University NHS Foundation Trust, Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sacha J","family":"Howell","sequence":"additional","affiliation":[{"name":"Wythenshawe Hospital Manchester Universities Foundation Trust, Wythenshawe, UK"},{"name":"Manchester Academic Health Science Centre, Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Pugh","sequence":"additional","affiliation":[{"name":"Manchester University Hospitals NHS Foundation Trust, Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8035-4471","authenticated-orcid":false,"given":"Claire","family":"Forde","sequence":"additional","affiliation":[{"name":"Clinical Genetics Service, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Howell","sequence":"additional","affiliation":[{"name":"Prevent Breast Cancer Centre, Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiona","family":"Lalloo","sequence":"additional","affiliation":[{"name":"Clinical Genetics Service, Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma Roisin","family":"Woodward","sequence":"additional","affiliation":[{"name":"Manchester Centre for Genomic Medicine, Central Manchester NHS Foundation Trust, Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2024,4,12]]},"reference":[{"key":"2025101713354070000_61.9.853.1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.21.02112"},{"key":"2025101713354070000_61.9.853.2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2017.7112"},{"key":"2025101713354070000_61.9.853.3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2005936"},{"key":"2025101713354070000_61.9.853.4","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1913948"},{"key":"2025101713354070000_61.9.853.5","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.ejca.2023.04.022","article-title":"Male breast cancer risk associated with pathogenic variants in genes other than Brca1\/2: an Italian case-control study","volume":"188","author":"Bucalo","year":"2023","journal-title":"Eur J Cancer"},{"key":"2025101713354070000_61.9.853.6","doi-asserted-by":"crossref","DOI":"10.3390\/cancers14133292","article-title":"Prevalence of cancer predisposition Germline variants in male breast cancer patients: results of the German consortium for hereditary breast and ovarian cancer","volume":"14","author":"Rolfes","year":"2022","journal-title":"Cancers (Basel)"},{"key":"2025101713354070000_61.9.853.7","doi-asserted-by":"crossref","DOI":"10.1186\/s12885-017-3631-8","article-title":"Chek2 C.1100Delc Mutation is associated with an increased risk for male breast cancer in Finnish patient population","volume":"17","author":"Hallamies","year":"2017","journal-title":"BMC 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