Continuation of HER2-targeted therapy using a permissive cardiotoxicity approach in patients with cancer therapy-related cardiac dysfunction

Background Cancer therapy-related cardiac dysfunction (CTR-CD) is a common complication of Human-Epidermal-growth-factor-Receptor 2 (HER2)-targeted therapy and may lead to interruption of cancer treatment. Contemporary guidelines support a permissive cardiotoxicity approach however real-world data are limited. Aim To evaluate heart failure management, cardiac outcomes and continuation of HER2-targeted therapy among patients with CTR-CD at a tertiary cardio-oncology centre. Methods We conducted a single-centre, prospective study of breast cancer patients receiving HER2-targeted therapy with CTR-CD between 2023 and 2025. Results A total of 16 consecutive patients were included (mean age 54±15 years, median follow-up 10.5 months [6.6,14.6]; 11 with stage II-III and 5 with stage IV breast cancer). Eleven patients received Trastuzumab and/or a trastuzumab-based antibody-drug conjugate (ADC), and 5 received Trastuzumab and/or a trastuzumab-based ADC with Pertuzumab. All patients had established CTR-CD at referral and 15 (94%) had prior anthracycline exposure. At referral, 8 patients (50%) had symptomatic CTR-CD (1 mild, 7 moderate), while 8 had asymptomatic disease (6 moderate, 2 severe). Median pre-HER2 therapy left ventricular ejection fraction (LVEF) was 59.5% [56.9,62.2], declining to a nadir of 45% [40,47.5] at a median of 7.5 months [5.3,9.8] after HER2 initiation. Heart failure therapy was initiated or intensified in 14 patients (88%). HER2 therapy was continued using a permissive cardiotoxicity approach in 5 patients with asymptomatic moderate CTR-CD, 1 with symptomatic mild CTR-CD, and 3 with symptomatic moderate CTR-CD. All patients with a treatment interruption (1 asymptomatic moderate CTR-CD, 2 symptomatic mild CTR-CD, 3 symptomatic moderate CTR-CD) were able to safely resume treatment after initiation of heart failure therapy, following a median interruption of 1.9 months [1.2, 2.9]. One patient with symptomatic CTR-CD subsequently required permanent cessation of HER2 therapy, while another required cessation during an initial treatment course but later recommenced and completed HER2-targeted therapy following disease progression. LVEF recovery occurred in 11 patients at a median of 3.1 months [2.4,7.5], including 5 during ongoing HER2 therapy, 3 during temporary treatment interruption, and 3 following completion of planned HER2 therapy. There were no cardiovascular hospitalisations or deaths. Conclusion A permissive cardiotoxicity approach supported by specialist cardio-oncology care appears safe and feasible in patients receiving HER2-targeted therapy who develop CTR-CD.