A patient receiving adjuvant trastuzumab develops a drop in left ventricular ejection fraction from 62% to 48% at 4 months of therapy. She is asymptomatic. Which statement best explains this finding and its management?
- A Irreversible dose-dependent myocyte death; trastuzumab must be stopped permanently
- B Type II reversible dysfunction from impaired HER2 signalling in cardiomyocytes; withhold trastuzumab and reassess after recovery ✓
- C Anthracycline-related free radical injury; switch to liposomal doxorubicin and continue trastuzumab
- D Coronary microvascular spasm; start calcium channel blockers and continue full-dose trastuzumab
Correct answer: B. Type II reversible dysfunction from impaired HER2 signalling in cardiomyocytes; withhold trastuzumab and reassess after recovery
Explanation
Trastuzumab causes type II chemotherapy-related cardiac dysfunction by blocking HER2 signalling needed for cardiomyocyte survival and repair. Unlike anthracycline injury, which destroys myocytes irreversibly, trastuzumab cardiotoxicity is largely reversible and responds to holding the drug and starting heart failure therapy, then rechallenging if LVEF recovers. This is why baseline and serial LVEF monitoring by echocardiography is mandatory during treatment, and why concurrent anthracyclines are avoided with trastuzumab.
Reference: Katzung's Basic and Clinical Pharmacology, 16th ed.
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