HER2-Targeted Therapy-From Pathophysiology to Clinical Manifestation: A Narrative Review

Area of Science:

• Cardio-oncology
• Molecular Cardiology
• Oncology

Background:

• Trastuzumab is a vital therapy for HER2-overexpressing breast cancer.
• Trastuzumab-induced cardiotoxicity (TIC) is a significant clinical concern.
• The precise mechanisms of TIC require further elucidation.

Purpose of the Study:

• To review the pathophysiological basis of TIC.
• To describe the clinical manifestations of TIC.
• To highlight the need for understanding TIC for improved patient outcomes.

Main Methods:

• Literature review of existing research on TIC.
• Analysis of molecular pathways affected by trastuzumab.
• Synthesis of clinical data on cardiac dysfunction.

Main Results:

• Trastuzumab inhibits the NRG-1/HER2/HER4 signaling pathway, affecting cardiomyocytes, endothelium, and cardiac progenitor cells.
• TIC involves immune cell activation, inflammation, and neurohormonal systems.
• Trastuzumab is associated with left ventricular systolic dysfunction, and potentially right ventricular damage and diastolic dysfunction.

Conclusions:

• Understanding TIC's pathophysiology is crucial for early detection and cardioprotective strategies.
• Further research is needed to establish a timeline of cardiac impairments for optimal cardioprotection timing.