Cardiotoxicity of HER2-directed therapies: impact on emergency department utilization in a real-world cohort of breast cancer patients

Background/Introduction Breast cancer (BC) is the most common malignant disease in women and subtype is a key prognostic factor. In HER2-positive disease, HER2-directed therapies are the mainstay of treatment, as they have yielded a massive improvement in long-term outcomes. On the downside, these drugs carry the risk of cardiotoxicity. Purpose This study aimed to assess the clinical implications of cardiac side effects in patients receiving HER2-directed therapy. Moreover, subtype-specific differences in emergency department (ED) presentation and 3-month mortality (3MM) of BC patients were investigated. Methods This single-centre retrospective study evaluated ED visits of breast cancer patients at an Austrian tertiary care centre. The frequency of ED visits due to cardiologic symptoms (decompensated heart failure, cardiomyopathy, arrhythmias [atrial fibrillation, unspecified tachycardia] and hypertensive derailment) in patients with and without HER2-directed therapy was investigated using a Chi Square test and a multinomial logistic regression controlling for age. Moreover, the overall frequency distribution of the breast cancer subtypes luminal A, luminal B/HER2-negative, luminal B/HER2-positive, HER2-positive (non-luminal) and triple negative were calculated. Subtype-specific 3MM rates were calculated for palliative and curative patients separately with a Chi-Square test. Results There was a total of 463 ED visits among 322 patients (curative setting: 94, palliative setting: 228) between 1st August 2016 and 31st December 2019. Median age was 62 years with a range of 25-95 years. A total of 68 patients had received HER2-directed therapy before ED visits. Active HER2-directed therapy was significantly associated with a higher rate of cardiologic ED visits (OR = 4.67, 95%CI [1.72; 10.02]). 56 % of these visits resulted in hospitalisation. Overall subtype distribution was as follows: 39 % (n = 126) luminal B/HER2-negative, 23 % (n = 74) triple negative, 19 % (n = 60) luminal B/HER2-positive, 10 % (n = 32) luminal A and 9 % (n = 30) HER2-positive (non-luminal). Breast cancer subtype was significantly associated with 3MM after ED visits in palliative patients (p = 0.006), with the highest mortality rate observed in triple negative disease (56%). Conclusion HER2-directed therapy significantly increased the risk of cardiologic emergency visits in this cohort of real-world cancer patients. These findings indicate the need for tailored cardio-oncology care strategies, including risk assessment, monitoring and cardioprotective interventions, to optimize tolerability, improve patients’ quality of life, and reduce healthcare burdens.