A 48-year-old woman receiving adjuvant trastuzumab for HER2-positive breast cancer develops dyspnoea and a drop in left ventricular ejection fraction from 62% to 45%. Which statement about this toxicity is correct?

• A It is usually irreversible and mandates permanent discontinuation of all HER2 therapy
• B It occurs more frequently than the cardiotoxicity produced by doxorubicin
• C It results from anthracycline-like free radical injury to cardiac myocytes
• D It is generally reversible on stopping the drug and improves with standard heart failure therapy ✓

Explanation

Trastuzumab inhibits HER2 signalling needed for cardiac myocyte survival and repair, causing a type II (non-dose-dependent) cardiomyopathy that is usually reversible with drug withdrawal and ACE inhibitors or beta blockers. This contrasts with anthracyclines, which cause dose-dependent, often irreversible type I injury through free radical generation and mitochondrial damage. Trastuzumab cardiotoxicity is less frequent than anthracycline cardiotoxicity, and concurrent anthracycline administration is avoided precisely because the combination multiplies risk.

Reference: Katzung Basic and Clinical Pharmacology, 15th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.