BACKGROUND: Despite advances in cancer treatment that have improved survival rates among patients with breast cancer, they are at high risk of developing cancer therapy-related cardiac dysfunction, which typically manifests as heart failure. Although exercise improves cardiorespiratory fitness in these patients, its effectiveness in preventing cancer therapy-related cardiac dysfunction remains unclear. OBJECTIVE: To assess the effectiveness of exercise-based interventions using cardiac function parameters and to identify the optimal exercise modality for preventing cancer therapy-related cardiac dysfunction. DESIGN: A systematic review and network meta-analysis. METHODS: A comprehensive search was conducted across PubMed, Embase, Scopus, Web of Science, and the Cochrane Library databases, covering all records from their inception through August 6, 2024. Studies that used exercise-based interventions, either exercise alone or with other interventions, were included. Those with insufficient data for the primary and secondary outcomes were excluded. Quality appraisal was evaluated using the risk of bias tool (RoB-2). All statistical analyses were conducted using the meta (version 7.0-0) and gemtc (version 1.0-2) packages in R software (version 4.3.3). For continuous outcomes, pairwise and network meta-analysis were employed to estimate mean differences (MDs) and 95 % confidence intervals (CI). The Surface Under the Cumulative Ranking Curve (SUCRA) was employed to rank treatments. The study protocol has been registered on PROSPERO (ID: CRD42024501160). RESULTS: In total, 13 randomized controlled trials involving 1122 participants were included in the review. There was low-to-high risk of bias across thirteen studies. Compared to usual care, exercise-based interventions significantly improved left ventricular ejection fraction (MD, 1.68
95 % CI, 0.59-2.77) and global longitudinal strain (MD, 1.40
95 % CI, 0.59-2.21). Based on the ranking probabilities, combined aerobic and resistance exercise was the most efficacious method for improving left ventricular ejection fraction (four studies
SUCRA, 0.96), followed by exercise-based cardio-oncology rehabilitation (two studies
SUCRA, 0.45) and aerobic exercise (four studies
SUCRA, 0.42). In terms of improving global longitudinal strain, combined aerobic and resistance exercise also ranked highest (three studies
SUCRA, 0.88). However, exercise-based cardio-oncology rehabilitation (two studies
SUCRA, 0.47) and aerobic exercise (one study
SUCRA, 0.45) were less effective. CONCLUSIONS: This network meta-analysis showed very low certainty for the prospective efficacy of exercise-based interventions, especially the combined aerobic and resistance exercise, in preventing cancer therapy-related cardiac dysfunction. Further rigorous studies are required to confirm the effectiveness of exercise-based interventions in preventing cancer therapy-related cardiac dysfunction among patients with breast cancer.