Long-term outcomes of prophylactic cardioprotection in early-stage breast cancer patients on non-anthracycline anti-HER2 therapy.

Anti-HER2 therapy has improved survival in HER2-positive breast cancer patients for decades but is associated with well-established cardiotoxicity. Our prior randomized controlled trial PROTECT HER2 found no short-term benefit of prophylactic beta-blocker cardio protection (CPT) based on changes in global longitudinal strain (GLS) in a breast cancer population treated with non-anthracycline anti-HER2 therapies. The long-term cardiovascular (CV) effects of CPT remain unknown. Utilizing the PROTECT HER2 cohort with 5-10 years follow-up, we performed a post hoc analysis to assess long-term outcomes. We evaluated the incidence of major adverse cardiovascular events (MACE; defined as all-cause mortality, stroke, myocardial infarction (MI), heart failure hospitalization (HFH), and significant arrhythmias) based on CPT. We also assessed associations between CV risk factors (hypertension, hyperlipidemia, diabetes and BMI≥25 kg/m2) and the occurrence of MACE. Among 109 patients the mean (SD) age was 51 (11) years, and the median (IQR) follow up was 7 (6-9) years post-RCT. Eight (7.3%) patients developed a total of 10 events, including 3 (2.8%) non-CV mortalities, 1 (0.9%) non-fatal stroke, and 6 (5.5%) arrhythmias. There were no significant associations observed between CV risk factors and MACE overall. However, 40% of patients (44/109) developed at least one new CV risk factor during follow-up. These findings demonstrate that while prophylactic CPT did not significantly impact long-term CV outcomes, a substantial proportion developed new risk factors over time, highlighting an important area for longitudinal risk monitoring and intervention.