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

SIMPLE SUMMARY: Trastuzumab administered as a (neo)adjuvant therapy in radically treated Human Epidermal Growth Factor Receptor 2 (HER2)-positive breast cancer patients improves overall survival. This study aimed to assess if factors commonly thought to play a role as biomarkers of trastuzumab-induced cardiotoxicity (TIC) are pathognomonic for this injury. Data obtained for 130 HER2-positive breast cancer patients do not support an influence of N-terminal brain natriuretic peptide (NT-proBNP), creatine kinase-MB (CK-MB), or myoglobin on the frequency of TIC. Suggestions for trastuzumab therapy include: close cooperation between cardiologists and oncologists; not using NT-proBNP, CK-MB, or myoglobin as standard TIC predictive markers; organizing prospective studies assessing the role of these parameters as TIC predictive markers in the case of HER2 blockage in conjunction with doublet immunotherapy or other anti-HER2 agents. 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.