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Therefore, we aimed to determine the correlation between a 22\u2010gene mutational profile and long\u2010term survival outcomes in patients with ER+\/ERBB2\u2010 EBC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and Methods<\/jats:title><jats:p>A total of 73 women diagnosed with ER+\/ERBB2\u2010 EBC between January 10, 2004, and June 2, 2008, were followed up until December 31, 2022. Univariate and multivariate Cox models were constructed to plot the relapse\u2010free survival (RFS) and overall survival (OS). The log\u2010rank test derived <jats:italic>p<\/jats:italic>\u2010value was obtained. For external validation, we performed a survival analysis of 1163 comparable patients retrieved from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>At follow\u2010up, 16 (21.9%) patients had relapsed, while 21 (nearly 29%) harbored mutant genes. Thirty\u2010three missense mutations were detected in 14 genes. The median ages were 51 and 46\u2009years in patients with and without mutations, respectively. Patients with any mutation had a 1.85\u2010fold higher risk of relapse (hazard ratio [HR]: 1.85, 95% confidence interval [CI]: 0.60\u20135.69) compared to those without any mutation. Patients who harbored any of the six genes (<jats:italic>MAP2K4, FGFR3, APC, KIT, RB1<\/jats:italic>, and <jats:italic>PTEN<\/jats:italic>) had a nearly 6\u2010fold increase in the risk of relapse (HR: 5.82, 95% CI: 1.31\u201318.56; <jats:italic>p<\/jats:italic>\u2009=\u20090.0069). Multivariate Cox models revealed that the adjusted HR for RFS and OS were 6.67 (95% CI: 1.32\u201327.57) and 8.31 (<jats:italic>p<\/jats:italic>\u2009=\u20090.0443), respectively. METABRIC analysis also demonstrated a trend to significantly worse RFS (<jats:italic>p<\/jats:italic>\u2009=\u20090.0576) in the subcohort grouped by having a mutation in any of the six genes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our single\u2010institution tissue bank study of Taiwanese women with ER+\/ERBB2\u2010 EBC suggests that a novel combination of six gene mutations might have prognostic capability for survival outcomes.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.70035","type":"journal-article","created":{"date-parts":[[2024,7,19]],"date-time":"2024-07-19T09:09:27Z","timestamp":1721380167000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Select gene mutations associated with survival outcomes in <scp>ER<\/scp>\u2010positive <scp>ERBB2<\/scp>\u2010negative early\u2010stage invasive breast cancer: A single\u2010institutional tissue bank study"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3440-8154","authenticated-orcid":false,"given":"Victor C.","family":"Kok","sequence":"first","affiliation":[{"name":"Division of Medical Oncology Kuang Tien General Hospital Cancer Center  Taichung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6870-8749","authenticated-orcid":false,"given":"To\u2010Yu","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Medical Research MacKay Memorial Hospital  New Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8712-8714","authenticated-orcid":false,"given":"Yi\u2010Chiung","family":"Hsu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Engineering National Central University  Taoyuan Taiwan"},{"name":"Center for Astronautical Physics and Engineering National Central University  Taoyuan Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuan\u2010Ching","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of General Surgery MacKay Memorial Hospital  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6226-2618","authenticated-orcid":false,"given":"Po\u2010Sheng","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of General Surgery MacKay Memorial Hospital  Taipei Taiwan"},{"name":"Department of Medicine Mackay Medical College  New Taipei 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