Exercise in regional breast cancer with neoadjuvant anthracycline-based chemotherapy with immune checkpoint-inhibition: study protocol for a prospective randomised controlled trial

Background: Anthracycline-based chemotherapy and immune checkpoint inhibition-increasingly used together in triple negative breast cancer (BC)-both cause cardiotoxicity and decline in peak oxygen consumption (VO2peak). While guidelines recommend exercise training for BC, the effectiveness of endurance, strength, and balance training during neoadjuvant immunochemotherapy remains unclear. Methods: The ExACT-ICI (Exercise in Regional Breast Cancer with adjuvant and neoadjuvant Anthracycline-based ChemoTherapy with Immune Checkpoint-Inhibition, NCT06672120) trial is a prospective single-center study randomizing regional TNBC patients (stage I-III, ages 18-65) receiving anthracycline chemotherapy plus pembrolizumab into exercise training (ET) or usual care groups. ET participants complete five weekly video-supervised sessions (endurance, resistance, balance) during 24-week treatment, monitored via smartwatch. Both groups undergo cardiopulmonary exercise testing, stress echocardiography, and strength/balance assessments at baseline, 6, 12, and 24 weeks. The primary outcome is VO2peak change from baseline to 24 weeks, with secondary outcomes including physical function, cardiac biomarkers, echocardiographic variables, quality of life, strength, balance, and exploratory cardiac adverse events through 52 weeks. Discussion and limitations: This study is the first to assess the effects of exercise intervention on VO2peak during immunochemotherapy in TNBC patients. Repetitive testing and smart watch monitoring will ensure optimized exercise prescription and safety during supervised, video-based training sessions. The study is limited to patients able to participate in online training sessions with a digital device.