A 52-year-old woman receiving weekly trastuzumab for HER2-positive breast cancer develops progressive dyspnoea. Echocardiography shows a left ventricular ejection fraction of 45%, reduced from 62% at baseline. She previously completed anthracycline-based chemotherapy four years ago without cardiac events. Which statement best explains her condition?
- A It is irreversible free-radical mediated myocardial injury, so trastuzumab must be stopped permanently
- B It reflects coronary vasospasm from anti-VEGF activity and responds to calcium channel blockers
- C It results from blockade of HER2 signalling needed for cardiac myocyte survival and is usually at least partially reversible ✓
- D It is immune-related myocarditis caused by T cell attack on cardiac myosin
Correct answer: C. It results from blockade of HER2 signalling needed for cardiac myocyte survival and is usually at least partially reversible
Explanation
HER2 signalling supports cardiac myocyte repair and survival, so trastuzumab causes type II (reversible) cardiotoxicity characterised by a fall in ejection fraction without structural myocyte death. Anthracycline toxicity is type I, dose dependent and largely irreversible due to free radical injury, which distinguishes it here. Immune checkpoint inhibitors, not trastuzumab, cause myocarditis. Trastuzumab can often be continued with heart failure therapy once the ejection fraction recovers.
Reference: Katzung's Basic and Clinical Pharmacology, 16th ed.
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Written and medically reviewed by the StethoPrep medical team.