Delayed Cardiac Dysfunction During Prolonged Use of Trastuzumab for the Treatment of HER2-Positive Metastatic Breast Cancer

Background: Cardiotoxicity is the most concerning side effect of trastuzumab in HER2-positive metastatic breast cancer. However, data on the delayed cardiac safety of long-term trastuzumab are rare. Patients and Methods: A retrospective review of patients with HER2-positive breast cancer receiving trastuzumab for more than 24 months in a metastatic setting was conducted. Patients with medical records of regular assessment of the left ventricular ejection fraction (LVEF) and serum brain natriuretic peptide (BNP) level were included. The incidence of cardiac events and possible predictive factors were analyzed. Results: A total of 75 patients were eligible for the current cardiac safety analyses. The median trastuzumab exposure was 50 (range: 29– 114) cycles. By the cut-off time, the median follow-up time for cardiotoxicity was 34.0 (range: 26.0– 41.9) months. The median timing of occurrence of a decrease in LVEF was 8.3 months after follow-up, mostly occurring within the third year from the initiation of trastuzumab. The cumulative incidence of LVEF decline was 10.7% (n=8) after 24-month trastuzumab. Patients with a history of anthracycline administration had a higher incidence of LVEF reduction (13.0% vs 3.6%, p =0.006). Five patients recovered soon after the cessation of trastuzumab. One patient died from congestive heart failure. BNP elevations were noted in 42.7% of patients, but elevated BNP levels could not identify patients with cardiotoxicity. Conclusion: Of the patients who had received long-term trastuzumab for more than 24 months, delayed cardiotoxicity was observed in only a small subset, and was reversible in most of them. Elevation of serum BNP could not predict cardiotoxicity. Less frequent LVEF monitoring could be considered during long-term use of trastuzumab.