Abstract
BACKGROUND AND OBJECTIVES: Dose-dense anthracycline-based chemotherapy has emerged as a critical strategy in managing high-risk breast cancer, offering survival benefits through increased dose intensity or shortened intervals. While short-term studies report preserved left ventricular ejection fraction (LVEF), the long-term cardiotoxicity of such regimens, especially at accelerated intervals, remains inadequately explored. Aim of this study was to evaluate the long-term cardiac safety of dose-dense anthracycline-based chemotherapy compared to conventional protocols in patients with non-metastatic breast cancer. METHODS: This retrospective study included 101 breast cancer patients treated at the National Center for Tumor Diseases, Heidelberg, between 2007 and 2014. Patients were classified into dose-dense (n=44) or conventional therapy (n=57) groups. Long-term follow-up (7-10 years post-treatment) comprised echocardiography with global longitudinal strain (GLS), electrocardiography, and cardiac biomarkers. Statistical analyses were conducted using Cox regression, and competing risks models. RESULTS: Left ventricular systolic function was preserved in both groups, with no significant differences in LVEF (58.1±5.4% in the dose-dense group and 59.6±3.7% in the conventional therapy group, p=0.341) or GLS. Diastolic dysfunction affected 28.6% of the dose-dense group and 47.4% of the conventional group, with age (odds ratio [OR], 1.14 per year; p=0.038) and hypertension (OR, 10.50; p=0.011) emerging as key predictors. Only one case of anthracycline-induced heart failure was reported. Mortality was primarily tumor-related, highlighting limited cardiac contributions to overall survival. CONCLUSIONS: Dose-dense anthracycline therapy demonstrated comparable long-term cardiac safety to conventional regimens, with preserved systolic function and minimal heart failure incidence. These findings underscore the importance of individualized risk assessment and comprehensive cardiac monitoring in breast cancer management.