Title : Early Preclinical Diagnosis of Trastuzumab induced Cardiotoxicity Among Breast Cancer Patients in West Virginia
Abstract:
The manifestation of cardiotoxicity induced by chemotherapeutic agents is a well-established pathophysiological consequence which may lead to chronic, progressive and often irreversible cardiac damage. While treatment options for breast cancer varies depending on the differentiated subtypes, trastuzumab remains one of the common therapeutic regimens, a humanized monoclonal antibody engineered to specifically target human epidermal growth factor receptor 2 (HER2) proteins. Trastuzumab related cardiotoxicity typically results in an overall decline in cardiac function, primarily characterized by reduction in left ventricular ejection fraction (LVEF) and development of symptoms associated with heart failure. Current strategies for the monitoring of cardiac function, during trastuzumab therapy, includes serial echocardiography, which is cost ineffective as well as offers limited specificity, while offering limited potential in monitoring early onset of cardiotoxicity. The prognostic approach using comprehensive assessment of panel of biomarkers is minimally invasive, highly cost effective and provides high specificity, proving to be a superior modality over conventionally utilized serial echocardiography. Hence, this study aims to develop a panel of novel biomarkers and circulating miRNAs for the early screening of trastuzumab induced cardiotoxicity. Patients with clinical diagnosis of invasive ductal carcinoma were enrolled in the study, with blood specimen collected and echocardiography performed prior to trastuzumab therapy initiation at baseline, 3- and 6-months post trastuzumab therapy. Following 6-months of trastuzumab therapy, about 18% of the subjects developed cardiotoxicity, as defined by reduction in LVEF. Our results showed significant upregulation of biomarkers and circulating miRNAs, specific to cardiac injury and remodeling, at 3- and 6-months post trastuzumab therapy. These biomarkers and circulating miRNAs significantly correlated with the cardiac injury specific markers, troponin I and T. The findings in the present study demonstrates the translational applicability of the proposed biomarker panel in early preclinical diagnosis of trastuzumab induced cardiotoxicity, further allowing management of cardiac function decline and improved health outcomes for breast cancer patients.
What will audience learn from your presentation?
- The present study demonstrates strong translational utility of the proposed biomarker panel in predicting early onset of trastuzumab induced cardiotoxicity in patients with breast cancer.
- The present study offers crucial evidence and a cost effective, non-invasive predictive modality demonstrating the efficacy of the proposed panel of biomarkers.
- The proposed panel offers a viable guide to the clinicians in developing mitigation strategies, including dose adjustments, mitigation of cardiovascular risks, or alternate treatment therapies.
- The implementation of this panel of biomarkers may improve health outcomes and reduce mortality associated with chemotherapy induced cardiotoxicity
