A 54-year-old woman on adjuvant trastuzumab for HER2-positive breast cancer develops progressive dyspnoea. Echocardiography shows a fall in left ventricular ejection fraction from 62% to 44% without regional wall motion abnormalities. The most likely mechanism of this toxicity is:
- A Inhibition of HER2 signalling required for cardiac myocyte survival and repair ✓
- B Irreversible anthracycline-type myocyte death due to free radical injury
- C Complement-mediated destruction of cardiac myocytes by the antibody
- D Coronary vasospasm caused by anti-VEGF activity
Correct answer: A. Inhibition of HER2 signalling required for cardiac myocyte survival and repair
Explanation
HER2 signalling is important for cardiac myocyte survival and adaptation to stress, so trastuzumab causes a reversible, dose-independent type II cardiomyopathy characterised by global decline in ejection fraction without the classic ultrastructural changes of anthracycline injury. Anthracyclines cause irreversible free radical mediated myocyte death; bevacizumab causes hypertension and thrombosis rather than vasospastic cardiomyopathy.
Reference: Katzung's Basic and Clinical Pharmacology, 16th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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