Permissive Cardiotoxicity in HER2-Positive Metastatic Breast Cancer With Moderate Left Ventricular Dysfunction

Permissive cardiotoxicity is increasingly recognized as important in human epidermal growth factor receptor 2 (HER2)-positive breast cancer, where oncologic benefits may outweigh cardiac risks.

A 49-year-old woman with HER2-positive, breast cancer gene 2-mutated metastatic breast cancer developed moderate left ventricular systolic dysfunction (ejection fraction 38%, global longitudinal strain -13.4%) and moderate-to-severe mitral regurgitation 4 months after initiating trastuzumab and pertuzumab. HER2 therapy was temporarily held, and guideline-directed medical therapy (GDMT) was initiated. After partial cardiac recovery, HER2-blockade was resumed under close surveillance. Her left ventricular ejection fraction improved to 52% (global longitudinal strain -17.5%) with GDMT despite continued HER2 therapy.

The decision to resume HER2 therapy was based on multidisciplinary consensus, incorporating partial cardiac recovery, absence of clinical congestive heart failure, and metastatic disease burden. GDMT enabled the safe resumption of HER2-blockade despite LVEF <40%.

Optimal GDMT supports cardiac recovery in patients with asymptomatic left ventricular dysfunction, allowing for continued HER2 therapy. Integrated cardio-oncology care is essential to balance cancer control with cardiovascular safety.