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dc.contributor.authorGoel, Shorn
dc.contributor.authorLiu, Jia
dc.contributor.authorGuo, Hao
dc.contributor.authorBarry, William
dc.contributor.authorBell, Richard
dc.contributor.authorMurray, Bronwyn
dc.contributor.authorLynch, Jodi
dc.contributor.authorBastick, Patricia
dc.contributor.authorChantrill, Lorraine
dc.contributor.authorKiely, Belinda E
dc.contributor.authorAbdi, Ehtesham
dc.contributor.authorRutovitz, Josie
dc.contributor.authorAsghari, Ray
dc.contributor.authorSullivan, Anne
dc.contributor.authorHarrison, Michelle
dc.contributor.authorKohonen-Corish, Maija
dc.contributor.authorBeith, Jane
dc.date.accessioned2020-02-14T01:52:15Z
dc.date.available2020-02-14T01:52:15Z
dc.date.issued2019
dc.identifier.issn2213-1779
dc.identifier.doi10.1016/j.jchf.2019.04.014
dc.identifier.urihttp://hdl.handle.net/10072/391462
dc.description.abstractObjectives: The aim of CATS (Cardiotoxicity of Adjuvant Trastuzumab Study) was to prospectively assess clinical, biochemical, and genomic predictors of trastuzumab-related cardiotoxicity (TRC). Background: Cardiac dysfunction is a common adverse effect of trastuzumab. Studies to identify predictive biomarkers for TRC have enrolled heterogeneous populations and yielded mixed results. Methods: A total of 222 patients with early-stage human epidermal growth factor receptor 2–positive breast cancer scheduled to receive adjuvant anthracyclines followed by 12 months of trastuzumab were prospectively recruited from 17 centers. Left ventricular ejection fraction (LVEF), troponin T, and N-terminal prohormone of brain natriuretic peptide were measured at baseline, post-anthracycline, and every 3 months during trastuzumab. Germline single-nucleotide polymorphisms in ERBB2, FCGR2A, and FCGR3A were analyzed. TRC was defined as symptomatic heart failure; cardiac death, arrhythmia, or infarction; a decrease in LVEF of >15% from baseline; or a decrease in LVEF of >10% to <50%. Results: TRC occurred in 18 of 217 subjects (8.3%). Lower pre-anthracycline LVEF and greater interval decline in LVEF from pre- to post-anthracycline were each associated with TRC on multivariate analyses (odds ratio: 3.9 [p = 0.0001] and 7.9 [p < 0.0001] for a 5% absolute change in LVEF). Higher post-anthracycline N-terminal prohormone of brain natriuretic peptide level was associated with TRC on univariate but not multivariate analyses. There were no associations between troponin T or ERBB2/FGCR polymorphisms and TRC. Baseline LVEF and LVEF change post-anthracycline were used to generate a “low-risk TRC score” to identify patients with low TRC incidence. Conclusions: Low baseline LVEF and greater LVEF decline post-anthracycline were both independent predictors of TRC. The other biomarkers did not further improve the ability to predict TRC. (Cardiotoxicity of Adjuvant Trastuzumab [CATS]; NCT00858039)
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherElsevier
dc.relation.ispartofpagefrom795
dc.relation.ispartofpageto804
dc.relation.ispartofissue9
dc.relation.ispartofjournalJACC: Heart Failure
dc.relation.ispartofvolume7
dc.subject.fieldofresearchCardiovascular medicine and haematology
dc.subject.fieldofresearchcode3201
dc.subject.keywordsScience & Technology
dc.subject.keywordsLife Sciences & Biomedicine
dc.subject.keywordsCardiac & Cardiovascular Systems
dc.subject.keywordsCardiovascular System & Cardiology
dc.subject.keywordsbiomarkers
dc.titleDecline in Left Ventricular Ejection Fraction Following Anthracyclines Predicts Trastuzumab Cardiotoxicity
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationGoel, S; Liu, J; Guo, H; Barry, W; Bell, R; Murray, B; Lynch, J; Bastick, P; Chantrill, L; Kiely, BE; Abdi, E; Rutovitz, J; Asghari, R; Sullivan, A; Harrison, M; Kohonen-Corish, M; Beith, J, Decline in Left Ventricular Ejection Fraction Following Anthracyclines Predicts Trastuzumab Cardiotoxicity, JACC: Heart Failure, 2019, 7 (9), pp. 795-804
dcterms.dateAccepted2019-04-02
dc.date.updated2020-02-14T01:50:23Z
gro.hasfulltextNo Full Text
gro.griffith.authorAbdi, Ehtesham


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