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We aimed to identify risk factors for trastuzumab-induced cardiotoxicity, with an emphasis on the HER2 Ile655Val single nucleotide polymorphism. This single-center case\u2013control study included 1056 patients with early-stage HER2 positive breast cancer that received adjuvant trastuzumab. Cardiotoxicity was defined as a decline in left ventricular ejection fraction (LVEF)\u2009&gt;\u200915% in patients without previous cardiomyopathy, or\u2009&gt;\u200910% in patients with baseline LVEF of\u2009&lt;\u200950%. Patient characteristics and cardiac parameters were compared in 78 (7.38%) cases and 99 randomly assigned controls, and the polymorphism was genotyped using real-time polymerase chain reaction. Cardiotoxicity was independently associated with advanced age (<jats:italic>P<\/jats:italic>\u2009=\u20090.024), lower body mass index (<jats:italic>P<\/jats:italic>\u2009=\u20090.023), left breast involvement (<jats:italic>P<\/jats:italic>\u2009=\u20090.001), N3 status (<jats:italic>P<\/jats:italic>\u2009=\u20090.004), diabetes (<jats:italic>P<\/jats:italic>\u2009=\u20090.016), and a family history of coronary artery disease (<jats:italic>P<\/jats:italic>\u2009=\u20090.019). Genotype distribution was as follows: A\/A (Ile\/Ile) was found in 111 (62.7%) patients, A\/G (Ile\/Val) in 60 (33.9%) patients, and G\/G (Val\/Val) in 6 (3.4%) patients. The genotype was not associated with cardiotoxicity or the severity of heart failure, reversibility, and recovery time. We found no association between the HER2 Ile655Val polymorphism and trastuzumab-induced cardiotoxicity; therefore, we do not recommend routine cardiotoxicity-risk stratification using this polymorphism.<\/jats:p>","DOI":"10.1038\/s41598-021-93634-6","type":"journal-article","created":{"date-parts":[[2021,7,13]],"date-time":"2021-07-13T10:24:02Z","timestamp":1626171842000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Influence of Ile655Val polymorphism on trastuzumab-induced cardiotoxicity in early-stage HER2 positive breast cancer"],"prefix":"10.1038","volume":"11","author":[{"given":"Ljubica","family":"Vazdar","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivo Darko","family":"Gabri\u0107","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivan","family":"Kruljac","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hrvoje","family":"Pintari\u0107","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"\u0160eparovi\u0107","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lora Stanka","family":"Kirigin Bilo\u0161","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mirjana","family":"Pavlovi\u0107","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"Te\u010di\u0107 Vuger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mario","family":"\u0160tefanovi\u0107","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,7,13]]},"reference":[{"key":"93634_CR1","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1016\/S0378-1119(98)00454-5","volume":"223","author":"U Vogt","year":"1998","unstructured":"Vogt, U. et al. 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