Trastuzumab (anti-HER2 monoclonal antibody) is used in HER2-overexpressing breast cancer. A patient develops trastuzumab-related cardiomyopathy. Unlike anthracycline cardiotoxicity, trastuzumab cardiac toxicity is:

• A Irreversible; trastuzumab permanently depletes cardiac neuregulin-1 leading to progressive cardiomyopathy
• B Largely reversible on drug discontinuation; HER2 signaling is required for cardiac repair, and blocking it impairs stress response rather than causing structural myocyte death ✓
• C Dose-cumulative; myocyte death is triggered at cumulative trastuzumab doses above 400 mg/m2
• D Mediated by immune complex deposition in cardiac microvasculature causing inflammatory cardiomyopathy

Explanation

Trastuzumab cardiotoxicity is mechanistically distinct from anthracyclines: anthracyclines generate free radicals causing permanent cardiomyocyte death (type I toxicity), while trastuzumab blocks HER2 signaling (neuregulin-1/ErbB2 pathway) that is essential for cardiac myocyte adaptation to stress and repair (type II toxicity). Trastuzumab cardiotoxicity is typically reversible upon drug withdrawal and management of heart failure, not associated with cumulative dose, and histology shows no permanent myocyte loss — this distinction has major clinical implications for rechallenge decisions.

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

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Written and medically reviewed by the StethoPrep medical team.