Effects of aerobic or resistance exercise on sleep and cancer-related fatigue in patients with breast cancer during or after neoadjuvant chemotherapy: a 3-arm randomized controlled trial

BACKGROUND: The aim of this secondary analysis of the BENEFIT randomized controlled trial was to investigate the effects of aerobic training (AT) or resistance training (RT) during neoadjuvant chemotherapy (NACT) on sleep and cancer-related fatigue (CRF), compared to a waitlist control group (WCG) that performed RT after surgery. METHODS: In the BENEFIT study, 184 patients with breast cancer with scheduled NACT (mean age = 50 years, standard deviation = 11) were randomized to AT (n = 62), RT (n = 62), or WCG (n = 60). While the AT and RT groups trained during NACT (two supervised and one home-based session weekly), the WCG completed the same training as the RT group but only after breast surgery. Self-reported sleep quality (Pittsburgh Sleep Quality Index) and CRF (EORTC QLQ-FA12) were collected before NACT (T0), after 9 weeks (T1), after NACT and before surgery (T2), 6 months after surgery (T3), and 12 months after surgery (T4). At T0, T2, and T3, sleep was additionally objectively measured by actigraphy. RESULTS: Longitudinal analyses of covariance examining changes from baseline suggested no clear difference of AT and RT compared to the WCG regarding sleep and CRF parameters post-intervention (T2). In contrast, at T3 the WCG, which exercised between T2 and T3, showed more favorable mean values compared to the AT group in total CRF (adjusted mean difference (AMD): - 10.53, 95% CI [- 19.63, - 1.42]) and physical CRF (AMD: - 14.28 [- 26.02, - 2.54] on 0-100 scale), and a tendency toward lower scores in self-reported global sleep quality (AMD: - 0.24 [- 0.48, 0.01] on log-transformed scale). Moderation analyses further suggested that group differences in total CRF at T3 in favor of the WCG were more pronounced among participants with at least mild emotional distress at baseline. There were no clear differences between groups in objective sleep parameters at T2 or T3, or regarding self-reported sleep or fatigue endpoints at T4. CONCLUSIONS: The findings suggest that exercise interventions in the post-NACT phase may be more effective than during NACT for managing fatigue, while providing limited benefits for sleep. TRIAL REGISTRATION: The BENEFIT study has been registered at ClincialTrials.gov (NCT02999074).