Decline in Left Ventricular Ejection Fraction Following Anthracyclines Predicts Trastuzumab Cardiotoxicity.

Goel, 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.

Goel, 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

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Publisher:: ELSEVIER SCI LTD
Publication Type:: Journal Article
Citation:: JACC. Heart failure, 2019, 7, (9), pp. 795-804
Issue Date:: 2019-09

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Field	Value	Language
dc.contributor.author	Goel, S
dc.contributor.author	Liu, J
dc.contributor.author	Guo, H
dc.contributor.author	Barry, W
dc.contributor.author	Bell, R
dc.contributor.author	Murray, B
dc.contributor.author	Lynch, J
dc.contributor.author	Bastick, P
dc.contributor.author	Chantrill, L
dc.contributor.author	Kiely, BE
dc.contributor.author	Abdi, E
dc.contributor.author	Rutovitz, J
dc.contributor.author	Asghari, R
dc.contributor.author	Sullivan, A
dc.contributor.author	Harrison, M
dc.contributor.author	Kohonen-Corish, M https://orcid.org/0000-0002-4073-1479
dc.contributor.author	Beith, J
dc.date.accessioned	2020-05-20T07:12:54Z
dc.date.available	2019-04-02
dc.date.available	2020-05-20T07:12:54Z
dc.date.issued	2019-09
dc.identifier.citation	JACC. Heart failure, 2019, 7, (9), pp. 795-804
dc.identifier.issn	2213-1779
dc.identifier.issn	2213-1787
dc.identifier.uri	http://hdl.handle.net/10453/140846
dc.description.abstract	OBJECTIVES: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.format	Print-Electronic
dc.language	eng
dc.publisher	ELSEVIER SCI LTD
dc.relation.ispartof	JACC. Heart failure
dc.relation.isbasedon	10.1016/j.jchf.2019.04.014
dc.rights	info:eu-repo/semantics/restrictedAccess
dc.subject	1102 Cardiorespiratory Medicine and Haematology
dc.title	Decline in Left Ventricular Ejection Fraction Following Anthracyclines Predicts Trastuzumab Cardiotoxicity.
dc.type	Journal Article
utslib.citation.volume	7
utslib.location.activity	United States
utslib.for	1102 Cardiorespiratory Medicine and Haematology
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney
utslib.copyright.status	closed_access	*
dc.date.updated	2020-05-20T07:12:51Z
pubs.issue	9
pubs.publication-status	Published
pubs.volume	7
utslib.start-page	795
utslib.citation.issue	9

Abstract:

OBJECTIVES: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).

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http://hdl.handle.net/10453/140846