Optimized exercise prescription for alleviating cancer-related fatigue in breast cancer survivors after primary treatment: a systematic review and dose-response network meta-analysis

Background: Cancer-related fatigue (CRF) significantly impairs the quality of life in breast cancer survivors. Although exercise is recommended in clinical guidelines to alleviate CRF, the effective and optimal doses remain uncertain. This study aims to examine the dose-response relationship of different exercise modalities with CRF in breast cancer survivors. Methods: Exercise dose was calculated as the product of duration, frequency, and intensity, expressed in metabolic equivalents of task minutes per week (METs-min/week), for comparison across studies. Bayesian network and dose-response meta-analyses were conducted to evaluate the impact of exercise on fatigue in breast cancer survivors and to model the nonlinear dose-response relationship. The certainty of the evidence was evaluated using the Confidence in Network Meta-Analysis (CINeMA) web application. Results: A total of 32 studies involving 2,067 patients were included. An inverted U-shaped dose-response relationship between overall exercise and CRF was observed; a minimum effective threshold could not be definitively established, with a peak effect at 730 METs-min/week (SMD = 1.32, 95% CrI: 0.78, 1.89), and effects were no longer significant beyond 1,100 METs-min/week. Meta-regression analyses indicated that baseline fatigue severity significantly moderated exercise effects. No other covariates showed significant moderation. Subgroup analyses suggested that interventions lasting less than 12 weeks were more effective. When stratified by modality, aerobic exercise (0-830 METs-min/week; very low certainty evidence), combined aerobic and resistance training (0-1,200 METs-min/week; low certainty evidence), resistance training (0-450 METs-min/week; low certainty evidence) and yoga (0-500 METs-min/week; low certainty evidence) all showed significant associations with CRF reduction. Conclusions: This study provides an evidence-based optimized range of exercise doses across different exercise types for alleviating CRF in breast cancer survivors. Considering the low and very low certainty of the evidence, further high-quality studies are needed to confirm these findings and refine clinical decision-making. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251146666, identifier: CRD420251146666.