{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,19]],"date-time":"2026-07-19T03:05:26Z","timestamp":1784430326561,"version":"3.55.0"},"reference-count":23,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2019,9,19]],"date-time":"2019-09-19T00:00:00Z","timestamp":1568851200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81772824"],"award-info":[{"award-number":["81772824"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic><jats:styled-content style=\"fixed-case\">BRCA<\/jats:styled-content>1\/2<\/jats:italic> genes are the most frequently germline mutated <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content>\u2010repair genes, and the survival of <jats:italic><jats:styled-content style=\"fixed-case\">BRCA<\/jats:styled-content>1\/2<\/jats:italic> carriers has been extensively explored in breast cancer. However, the prevalence of germline mutations in non\u2010<jats:italic><jats:styled-content style=\"fixed-case\">BRCA<\/jats:styled-content>1\/2 <\/jats:italic><jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content>\u2010repair genes and the survival of carriers are largely unknown in a large cohort of unselected breast cancer patients. Germline mutations in 16 <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content>\u2010repair genes were determined using a multigene panel in 7657 <jats:italic><jats:styled-content style=\"fixed-case\">BRCA<\/jats:styled-content>1\/2<\/jats:italic>\u2010negative breast cancer patients who were unselected for family history of cancer or age at diagnosis. Among the 7657 <jats:italic><jats:styled-content style=\"fixed-case\">BRCA<\/jats:styled-content>1\/2<\/jats:italic>\u2010negative breast cancer patients, 257 (3.4%) carried at least 1 pathogenic germline mutation in the 16 <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content>\u2010repair genes. The prevalence of <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content>\u2010repair gene mutations was significantly higher in familial breast cancers (5.2%, <jats:italic>P\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>0.002) and early\u2010onset breast cancers (diagnosed at and before the age of 40) (4.5%, <jats:italic>P\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>0.003) than that of sporadic breast cancers (2.9%) (diagnosed above age of 40), respectively. The <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content>\u2010repair gene mutation carriers were significantly more likely to have a larger tumor (<jats:italic>P\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>0.04) and axillary lymph node metastasis (<jats:italic>P\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>0.03). Moreover, <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content>\u2010repair gene mutation was an independent unfavorable factor for recurrence\u2010free survival (adjusted hazard ratio [<jats:styled-content style=\"fixed-case\">HR<\/jats:styled-content>]\u00a0=\u00a01.38, 95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>: 1.00\u20101.91, <jats:italic>P\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>0.05) and disease\u2010specific survival (adjusted <jats:styled-content style=\"fixed-case\">HR<\/jats:styled-content>=1.63, 95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>: 1.04\u20102.57, <jats:italic>P\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>0.03) in this cohort. Overall, 3.4% of <jats:italic><jats:styled-content style=\"fixed-case\">BRCA<\/jats:styled-content>1\/2<\/jats:italic>\u2010negative breast cancer patients carried germline mutations in the 16 <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content>\u2010repair genes, and the <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content>\u2010repair gene mutation carriers exhibited an aggressive phenotype and had poor survival compared with noncarriers.<\/jats:p>","DOI":"10.1111\/cas.14175","type":"journal-article","created":{"date-parts":[[2019,8,21]],"date-time":"2019-08-21T06:49:06Z","timestamp":1566370146000},"page":"3368-3374","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Germline mutation in <scp>DNA<\/scp>\u2010repair genes is associated with poor survival in <i><scp>BRCA<\/scp>1\/2\u2010<\/i>negative breast cancer patients"],"prefix":"10.1111","volume":"110","author":[{"given":"Zhenhua","family":"Fan","sequence":"first","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Breast Center, Beijing Cancer Hospital and Institute Peking University Cancer Hospital Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Hu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Breast Center, Beijing Cancer Hospital and Institute Peking University Cancer Hospital Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Ouyang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Breast Center, Beijing Cancer Hospital and Institute Peking University Cancer Hospital Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinfeng","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Breast Center, Beijing Cancer Hospital and Institute Peking University Cancer Hospital Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianfeng","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Breast Center, Beijing Cancer Hospital and Institute Peking University Cancer Hospital Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoqing","family":"Fan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Breast Center, Beijing Cancer Hospital and Institute Peking University Cancer Hospital Beijing 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