Trastuzumab (Herceptin) is used in HER2-positive breast cancer. Its mechanism of cardiotoxicity (asymptomatic LV dysfunction/heart failure) differs from anthracycline cardiotoxicity because trastuzumab-associated dysfunction is:

• A Cumulative, dose-dependent, and irreversible due to reactive oxygen species-mediated cardiomyocyte necrosis
• B Generally reversible and not dose-cumulative, as HER2 signalling is required for cardiomyocyte survival repair and its disruption causes reversible contractile dysfunction ✓
• C Due to immune complex deposition in myocardial capillaries causing type III hypersensitivity
• D Caused by direct monoclonal antibody binding to cardiac myosin heavy chains

Explanation

Anthracycline cardiotoxicity is cumulative, dose-dependent, and largely irreversible, caused by iron-mediated reactive oxygen species that destroy cardiomyocytes. Trastuzumab-associated cardiac dysfunction is characteristically non-cumulative, not dose-dependent, and largely reversible upon drug discontinuation because HER2 (ErbB2) signalling is a key survival and repair pathway in cardiomyocytes; its blockade impairs compensatory repair rather than causing direct cytotoxic death. This distinction is clinically important as trastuzumab can often be restarted after cardiac recovery, unlike anthracyclines after significant cumulative dose.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.