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)
N-terminal prohormone of brain natriuretic peptide
OR
odds ratio
ROC
receiver operating characteristic
SNP
single-nucleotide polymorphism
TnT
troponin T
TRC
trastuzumab-related cardiotoxicity
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This project was funded by the National Breast Cancer Foundation of Australia (Novel Concept Award NC-08-03). Dr. Goel has received laboratory research funding from Eli Lilly; conducts clinical research sponsored by Eli Lilly and Novartis; and has served on advisory boards for Eli Lilly, Novartis, and G1 Therapeutics. Dr. Liu has received clinical research support from AstraZeneca. Dr. Chantrill serves on the advisory board for Merck, Sharp & Dohme; and has received travel reimbursement from Amgen Australia. Dr. Harrison serves on an advisory board for AstraZeneca; has received travel reimbursement from AstraZeneca; and has received paid honoraria from AstraZeneca and Roche. Dr. Beith serves on advisory boards for Roche, Novartis, Pfizer, and Lilly. Dr. Sullivan has passed away and is unable to provide a disclosure statement. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
