ICARE-TNBC : Immune checkpoint-associated cardiotoxicity risk evaluation in early-stage triple-negative breast cancer

Abstract

Triple-negative breast cancer (TNBC) is a particularly aggressive subtype that predominantly affects younger women. Pembrolizumab combined with chemotherapy improves outcomes in TNBC. However, anthracyclines, pembrolizumab and radiotherapy are potentially cardiotoxic but cardiovascular safety data in routine practice are limited. To describe cardiotoxicity and investigate predictive factors in patients treated with pembrolizumab, with or without anthracyclines, for early-stage TNBC. We hypothesised that baseline cardiovascular risk factors would predict cardiotoxicity. We conducted a single-centre, retrospective observational study including 61 patients with triple-negative breast cancer treated between January 2022 and November 2024. The primary endpoint was a composite cardiotoxicity outcome defined according to ESC guidelines as cardiovascular death, cardiac dysfunction, myocarditis, pericarditis, arrhythmia or conduction disorder, acute coronary syndrome (ACS), or ischaemic stroke. Predictors were assessed using univariable Cox models; overall survival by Kaplan–Meier and log-rank, and cardiotoxicity incidence by cumulative incidence with competing risk of non-cardiovascular death. Among the 61 patients (mean age 55 ± 13 years), 33% were obese, 23% had hypertension, and 23% had dyslipidaemia. After a median follow-up of 14 months (IQR 10–21), cardiotoxicity occurred in 13% of patients with a median onset time of 6 (IQR 3–8) months. No cases of cardiovascular death were observed. 7% of patients presented with cardiac dysfunction, 2% with myocarditis, 2% with atrial fibrillation, 2% with ACS, and 2% with ischaemic stroke. Patients with cardiotoxicity had a higher rate of all-cause death than patients without cardiotoxicity (29% vs 4%; p<0.001). In univariable analysis, predictors of cardiotoxicity were age (HR 1.07; 95% CI 1.00–1.13; p=0.036), family history of coronary artery disease (HR 9.17; 95% CI 1.10–76.2; p=0.040), hypertension (HR 6.01; 95% CI 1.43–25.4; p=0.015), and reduced estimated glomerular filtration rate (HR 1.5; 95% CI 1.11–2.07; p=0.008). In patients with early-stage TNBC treated with pembrolizumab, cardiotoxicity was frequent and associated with a significant reduction in overall survival. Larger prospective studies are required to better characterise predictors of cardiotoxicity in this setting.Annualised all-cause death events  Cardiotoxicity by hypertension