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

Abstract

Cardiotoxicity induced by breast cancer therapies is a potentially serious complication associated with the use of various breast cancer therapies. Prediction and better management of cardiotoxicity in patients receiving chemotherapy is of critical importance. However, the management of cancer therapy-related cardiac dysfunction (CTRCD) lacks clinical evidence and is based on limited clinical studies. Aim: To provide an overview of existing and potentially novel biomarkers that possess a promising predictive value for the early and late onset of CTRCD in the clinical setting. Methods: A systematic review of published studies searching for promising biomarkers for the prediction of CTRCD in patients with breast cancer was undertaken according to PRISMA guidelines. A search strategy was performed using PubMed, Google Scholar, and Scopus for the period 2013–2023. All subjects were >18 years old, diagnosed with breast cancer, and received breast cancer therapies. Results: The most promising biomarkers that can be used for the development of an alternative risk cardiac stratification plan for the prediction and/or early detection of CTRCD in patients with breast cancer were identified. Conclusions: We highlighted the new insights associated with the use of currently available biomarkers as a standard of care for the management of CTRCD and identified potentially novel clinical biomarkers that could be further investigated as promising predictors of CTRCD.

Cardiovascular Biomarkers in Cardio-Oncology: Antineoplastic Drug Cardiotoxicity and Beyond

“…However, troponins and natriuretic peptides have been indicated in the last ESC Guidelines on Cardio-Oncology as risk factors to be evaluated as part of the baseline cardiotoxicity risk assessment because of their usefulness as indicators of cardiomyocyte injury, but their predictive capacity for the onset of cardiotoxicity still lacks reliability. Predictive biomarkers for the early and late onset of CTRCD are urgently needed to mitigate the risks associated with cardiac complications [121] Novel emerging biomarkers were recently evaluated in a CTRCD setting.…”

“…However, further studies are needed to accurately evaluate the potential use of miRNAs in this clinical setting. -Myeloperoxidase (MPO): myeloid-lineage-restricted enzyme with bactericidal properties, found in the azurophilic granules of neutrophils, involved in the neutrophil extracellular traps (NETs) that are implicated in myocardial infarction and in serious cardiovascular events [121]. Elevated circulating levels of MPO were found in breast cancer patients that experienced cardiotoxicity, so MPO is now considered a promising biomarker for the early detection of anthracycline-related and anthracyclinetrastuzumab cardiac dysfunction, based on the results of several studies [125,126].…”

“…-Other Biomarkers under Investigation: other potentially promising biomarkers are currently under investigation for their utility in the detection and/or prediction of CTRCD. These include endothelin-1, neuregulin-1, plasma bioactive adrenomedullin (ADM), D-dimer, soluble fms-like tyrosine kinase receptor (sFlt)-1, soluble ST2 (sST2), CK-MB, topoisomerase II α gene (TOP2A), cardiac myosin light chain 1 (cMLC-1), vascular endothelial growth factor (VEGF), placental growth factor (PIGF), procollagen-derived type-I C-terminal-propeptide (PICP), epicardial adipose tissue (EAT) volume, circulating bilirubin, hemopexin, glycated hemoglobin (HbA(1)c), advanced oxidation protein products (AOPP), human resistin and vascular adhesion molecule 1 (VCAM-1) [121].…”