Prospective and Molecular Biomarker-Based Evaluation of Cardiac Side Effects in Patients With Early-Stage Breast Cancer Receiving Systemic Therapy: A Single-Center Observational Cohort Study

Background:

Anthracyclines and anti-HER2 agents are cornerstone treatments for early-stage breast cancer but carry meaningful risk of cancer therapy-related cardiac dysfunction (CTRCD). Cardiotoxicity is often initially subclinical, with left ventricular ejection fraction (LVEF) decline appearing late, after irreversible myocardial damage may have occurred. The 2022 European Society of Cardiology (ESC) Cardio-Oncology Guidelines recommend Global Longitudinal Strain (GLS) as a more sensitive parameter than LVEF for early detection of cardiac dysfunction. A relative reduction in GLS can occur weeks to months before clinically apparent LVEF decline.

While echocardiography provides functional assessment of the heart, it offers limited insight into the molecular mechanisms underlying cardiac injury. Circulating microRNAs (miRNAs) are emerging as candidate biomarkers reflecting cardiomyocyte injury, oxidative stress, and fibrosis. Although several studies have evaluated cardiotoxicity from anthracyclines and anti-HER2 therapies, most have been retrospective and focused solely on LVEF changes. Prospective studies that simultaneously assess GLS and circulating miRNAs are limited, as are head-to-head comparisons of cardiac effects across different chemotherapy regimens at both functional and molecular levels.

Rationale:

This study addresses these gaps by evaluating cardiac effects of systemic therapy in early-stage breast cancer patients using both functional (echocardiographic) and molecular (miRNA) parameters in a prospective design. The findings are expected to contribute to early identification of cardiotoxicity, identification of high-risk patient subgroups, and development of personalized cardio-oncology surveillance strategies.