A 46-year-old woman receiving adjuvant trastuzumab after anthracycline-based chemotherapy presents at month six with exertional dyspnoea. Echocardiography shows the LVEF has fallen from 62% to 46%. Which statement best characterises this complication?
- A It is an irreversible dilated cardiomyopathy identical to late anthracycline injury
- B It results from loss of HER2 signalling in cardiac myocytes and is often reversible on stopping the drug ✓
- C It represents acute rheumatic valvulitis triggered by monoclonal antibody therapy
- D It is a hypersensitivity myocarditis requiring lifelong corticosteroids
Correct answer: B. It results from loss of HER2 signalling in cardiac myocytes and is often reversible on stopping the drug
Explanation
Trastuzumab inhibits HER2, which in the heart mediates survival signalling in myocytes exposed to stress. Blocking it causes a type II, dose-independent cardiotoxicity characterised by declining LVEF, which is why baseline and periodic echocardiographic monitoring is mandatory during treatment. Unlike anthracyclines, which cause dose-dependent, largely irreversible free-radical myocyte injury, trastuzumab-related dysfunction frequently recovers after withholding the drug, and rechallenge may be possible.
Reference: Katzung Basic and Clinical Pharmacology, 16th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.