Biomarkers of Trastuzumab-Induced Cardiac Toxicity in HER2- Positive Breast Cancer Patient Population

Abstract

Trastuzumab-induced cardiotoxicity (TIC) can lead to early treatment discontinuation. The aim of this study was to evaluate: N-terminal brain natriuretic peptide (NT-proBNP), creatine kinase-MB (CK-MB), myoglobin, and selected biochemical and clinical factors as predictors of TIC. One hundred and thirty patients with HER2-positive BC receiving adjuvant trastuzumab therapy (TT) were enrolled. Measurement of cardiac markers and biochemical tests as well as echocardiography were performed prior to TT initiation and every three months thereafter. Cardiotoxicity leading to treatment interruption occurred in 24 patients (18.5%). While cardiotoxicity caused early treatment discontinuation in 14 patients (10.8%), the TIC resolved in 10 (7.7%) and TT was resumed. The most common complication was a decrease in left ventricular ejection fraction of more than 10% from baseline or below 50% (7.7%). In patients with TIC, there was no increase in the levels of NT-proBNP, myoglobin, and CK-MB. BMI, hypertension, ischemic heart disease, diabetes, age, cancer stage, type of surgery, use of radiotherapy, chemotherapy, and hormone therapy were shown to not have an effect on TIC occurrence. NT-proBNP, myoglobin, and CK-MB are not predictors of TIC. There is an ongoing need to identify biomarkers for TIC.

Cardioprotective Agents for the Primary Prevention of Trastuzumab-Associated Cardiotoxicity: A Systematic Review and Meta-Analysis

“…The evaluation of these cardiac biomarkers is theoretically an important component for monitoring of patients undergoing trastuzumab chemotherapy, since they provide evidence of even subtle cardiac dysfunction, before it becomes obvious in echocardiography. Thereby, several prospective studies [ 43 , 44 , 45 , 46 , 47 ] have proposed those cardiac biomarkers, as surrogate indices of cardiotoxicity with controversial results. In our systematic review, we attempted to evaluate the impact of ACEIs/ARBs and or BBs on the aforementioned biomarkers.…”

New Insights in the Era of Clinical Biomarkers as Potential Predictors of Systemic Therapy-Induced Cardiotoxicity in Women with Breast Cancer: A Systematic Review

“…The studies focusing on the role of natriuretic peptides (NPs) in predicting and/or detecting CTRCD in breast cancer patients [ 86 , 87 , 90 , 91 , 92 , 96 , 97 , 98 , 99 , 100 , 101 , 103 , 105 , 106 , 109 , 113 , 114 , 117 , 118 , 119 , 122 , 123 , 124 , 125 , 126 , 127 , 128 , 129 , 130 , 131 , 132 , 133 , 134 , 135 , 136 , 137 , 138 , 139 , 140 , 141 , 142 , 143 , 144 , 145 ], as identified in the review, are shown in Table S1 .…”

“…In addition to above-mentioned biomarkers, other potentially promising biomarkers are currently under investigation for their utility in the detection and/or prediction of CTRCD including: coronary artery calcification [ 298 ], endothelin-1 [ 299 ], neuregulin-1 [ 285 , 300 ], plasma bioactive adrenomedullin (ADM) [ 301 ], fragmented QRS (fQRS) [ 302 ], D-dimer [ 303 ], soluble fms-like tyrosine kinase receptor (sFlt)-1 [ 105 ], soluble ST2 (sST2) [ 145 , 149 , 171 , 279 , 304 ], CK-MB [ 134 , 286 ], topoisomerase II α gene ( TOP2A ) [ 305 ], cardiac myosin light chain 1 (cMLC-1) [ 306 ], vascular endothelial growth factor (VEGF) [ 93 ], placental growth factor (PIGF) [ 93 , 98 ], procollagen-derived type-I C-terminal-propeptide (PICP) [ 307 ], epicardial adipose tissue (EAT) volume [ 308 , 309 ], circulating bilirubin [ 310 ], hemopexin [ 311 ], glycated hemoglobin (HbA(1)c) [ 103 ], advanced oxidation protein products (AOPP) [ 102 ], human resistin [ 312 ] and vascular adhesion molecule 1 (VCAM-1) [ 117 ].…”

Mutation of PTEN: Loss and Likelihood of Being a Non-responder to Trastuzumab in a Sample of Iraqi Her2+ Breast Cancer Patients

“…There is no evidence to support the use of cardiovascular biomarkers such as NT-pro BNP, CK-MB, or myoglobin to anticipate the onset of cardiovascular issues. The challenge is to treat BC effectively while limiting toxicity [ 22 ]. According to the results of the present study, non-responsive women demonstrated a higher frequency of PTEN loss compared with responsive women.…”