{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:21:49Z","timestamp":1790835709147,"version":"4.1.0"},"reference-count":26,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2020,1,28]],"date-time":"2020-01-28T00:00:00Z","timestamp":1580169600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,1,28]],"date-time":"2020-01-28T00:00:00Z","timestamp":1580169600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Myriad Genetics Inc","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Breast Cancer Res Treat"],"published-print":{"date-parts":[[2020,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n<jats:title>Purpose<\/jats:title>\n<jats:p>Compared to breast cancer risk genes such as <jats:italic>BRCA2<\/jats:italic>, <jats:italic>ATM<\/jats:italic>, <jats:italic>PALB2,<\/jats:italic> and <jats:italic>NBN<\/jats:italic>, no defined phenotype is currently associated with biallelic pathogenic variants (PVs) in <jats:italic>CHEK2<\/jats:italic>. This study compared the prevalence of breast and other cancers in women with monoallelic and biallelic <jats:italic>CHEK2<\/jats:italic> PVs.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p><jats:italic>CHEK2<\/jats:italic> PV carriers were identified through commercial hereditary cancer panel testing (09\/2013\u201307\/2019). We compared cancer histories of 6473 monoallelic carriers to 31 biallelic carriers. Breast cancer risks were estimated using multivariate logistic regression and are reported as odds ratios (OR) with 95% confidence intervals (CI).<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>Breast cancer frequency was higher among biallelic <jats:italic>CHEK2<\/jats:italic> PV carriers (80.6%, 25\/31) than monoallelic carriers (41.2%, 2668\/6473; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001). Biallelic carriers were more likely to be diagnosed at or before age 50 (61.3%, 19\/31) and to have a second breast cancer diagnosis (22.6%, 7\/31) compared to monoallelic carriers (23.9%, 1548\/6473; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001 and 8.1%, 523\/6473; <jats:italic>p<\/jats:italic>\u2009=\u20090.0107, respectively). Proportionally more biallelic carriers also had any cancer diagnosis and\u2009&gt;\u20091 primary diagnosis. Compared to women with no PVs, biallelic PV carriers had a higher risk of developing ductal invasive breast cancer (OR 8.69, 95% CI 3.69\u201320.47) and ductal carcinoma in situ (OR 4.98, 95% CI 2.00\u201312.35) than monoallelic carriers (OR 2.02, 95% CI 1.90\u20132.15 and OR 1.82, 95% CI 1.66\u20132.00, respectively).<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>These data suggest that biallelic <jats:italic>CHEK2<\/jats:italic> PV carriers have a higher risk for breast cancer, are more likely to be diagnosed younger, and to have multiple primary breast cancers compared to monoallelic carriers. Biallelic carriers also appear to have a higher risk of cancer overall. Therefore, more aggressive management may be appropriate for women with biallelic PVs in <jats:italic>CHEK2<\/jats:italic> compared with current recommendations for monoallelic carriers.<\/jats:p>\n<\/jats:sec>","DOI":"10.1007\/s10549-020-05543-3","type":"journal-article","created":{"date-parts":[[2020,1,28]],"date-time":"2020-01-28T13:02:50Z","timestamp":1580216570000},"page":"503-509","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["High risk of breast cancer in women with biallelic pathogenic variants in CHEK2"],"prefix":"10.1007","volume":"180","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5865-3467","authenticated-orcid":false,"given":"Irene","family":"Rainville","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanell","family":"Hatcher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Rosenthal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie","family":"Larson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Bernhisel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Meek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi","family":"Gorringe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin","family":"Mundt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Manley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,1,28]]},"reference":[{"issue":"4","key":"5543_CR1","doi-asserted-by":"publisher","first-page":"542","DOI":"10.1200\/JCO.2007.12.5922","volume":"26","author":"M Weischer","year":"2008","unstructured":"Weischer M, Bojesen SE, Ellervik C, Tybj\u00e6rg-Hansen A, Nordestgaard BG (2008) CHEK2*1100delC genotyping for clinical assessment of breast cancer risk: meta-analyses of 26,000 patient cases and 27,000 controls. 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All patients provided informed consent for clinical testing. De-identified clinical information was obtained from provider-completed test request forms (TRFs). Data were included only for women residing in states with no legal prohibitions on the use of de-identified data for research purposes. Only aggregate data are presented in the manuscript. Therefore, this analysis did not meet the U.S. Health and Human Services definition of research on human subjects (HHS 46.102) and did not require Institutional Review Board approval.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval and informed consent"}}]}}