New onset of left ventricular dysfunction and diastolic dysfunction are uncommon in patients with her2+ breast cancer after completion of cancer therapy

Abstract Background Cardiotoxicity from anthracyclines and trastuzumab is common among patients with breast cancer during therapy. However, there are limited data on new onset of cardiotoxicity (systolic or diastolic dysfunction) after completion of therapy. This knowledge has implications to guide long-term follow-up. Purpose The aim of this study was to evaluate the incidence of cancer therapy related cardiac systolic dysfunction (CTRCD) and diastolic dysfunction (DD) in women with HER2+ breast cancer after completion of cancer therapy and compare to incidence during cancer therapy. Methods We conducted a prospective cohort study of women with HER2+ breast cancer who were treated with sequential anthracycline and trastuzumab therapy, with or without radiation therapy (The EMBRACE-MRI trial, NCT02306538). Comprehensive surveillance echocardiograms were performed at baseline and every 3 months during treatment, early post-trastuzumab, then at years 1, 2, and 3 post trastuzumab completion. CTRCD was defined as a reduction in 3D-left ventricular ejection fraction (LVEF) by ≥ 10% from baseline to < 55%. Diastolic dysfunction was defined as per the American Society of Echocardiography guidelines. Results A total of 136 female patients, with a mean age of 51.1 ± 9.2 years were recruited. Among them, 15.4% had hypertension, 3.7% had diabetes mellitus, and 10.3% had dyslipidemia. The mean cumulative doxorubicin equivalent dose was 203.9 ± 12.5 mg/m2, 120 patients received radiation therapy with the mean heart dose of 170.8 ± 75.9 cGy. During cancer treatment, 27 out of 136 patients (19.9%) developed CTRCD. In long-term follow-up, due to death or interruption due to the COVID-19 pandemic, follow-up was available in 128 patients at 1 year, 117 at 2 years and 111 at 3 years. 5 of the 27 patients still had persistent LV dysfunction (3 at 1 year, 1 at 2 year and 1 at 3 year), however, there were no new diagnosis of CTRCD post completion of therapy. Of 129 patients with baseline normal or indeterminate diastolic function, new DD was identified in 25/129 patients (19.4%) during cancer treatment (17 grade I, 2 grade II, 6 unable to grade). After completion of cancer therapy, 5 patients had persistent DD. In patients with no DD during therapy and completed 3 year follow-up, 5 patients developed new DD after therapy (2 grade I, 3 unable to grade). Figure 1 illustrates the percentage of patients with new CTRCD or new diastolic dysfunction at each timepoint. None of the patients developed clinical heart failure. Conclusion Although both CTRCD and diastolic dysfunction are common during sequential therapy with anthracyclines and trastuzumab in women with HER2+ breast cancer, new onset after treatment completion is rare during a careful follow-up. These findings have implications for long-term surveillance.