A 62-year-old woman on adjuvant trastuzumab for HER2-positive breast cancer presents with exertional dyspnoea. Echocardiography shows a drop in left ventricular ejection fraction from 62 percent to 44 percent. The cardiac toxicity of trastuzumab differs from doxorubicin because it is:

• A Prevented by co-administration of dexrazoxane
• B Cumulative, dose-related and irreversible
• C Due to iron deposition in myocardial cells
• D Dose-independent and usually reversible on stopping the drug ✓

Explanation

Trastuzumab inhibits HER2 signalling required for cardiomyocyte survival and repair, producing a type II cardiotoxicity that is not dose-cumulative and typically improves after withdrawal. Doxorubicin causes type I injury through free radical generation and mitochondrial damage, which is cumulative and often irreversible; dexrazoxane protects against anthracycline, not trastuzumab, toxicity. Risk rises when trastuzumab follows anthracycline exposure.

Reference: Katzung Basic and Clinical Pharmacology, 16th ed.

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