Structured exercise improves fatigue and health-related quality of life in metastatic breast cancer patients: the multinational randomized controlled preferable-effect study

INTRODUCTION & AIMS Exercise has been proven safe and effective for patients with breast cancer in the curative setting, however evidence in patients with metastatic breast cancer (mBC) is scarce. The aim of the PREFERABLE - EFFECT study (NCT04120298) was to evaluate the effects of a structured exercise program on fatigue, health-related quality of life (HRQoL), and other cancer- and treatment-related side effects in patients with mBC. METHODS The randomized controlled trial included patients with mBC from five European countries (Germany, Spain, Netherlands, Poland, Sweden) and Australia. Participants were randomly assigned to usual care (UC) or a 9-month supervised and individualized exercise program (EX) involving twice weekly aerobic, resistance, and balance exercises. The primary outcomes, physical fatigue (EORTC QLQ-FA12 subscale) and HRQoL (EORTC QLQ-C30 summary score) were assessed at baseline, 3, 6, and 9 months. Among other physical fitness outcomes, maximal short exercise capacity was assessed with the Steep Ramp Test. Changes from baseline to 3, 6 (primary endpoint) and 9 months were compared between groups using adjusted mixed models for repeated measures. RESULTS A total of 357 patients were randomized (EX=178, UC=179). On average, participants were 55.4 years of age (SD=11.1) and 73.9% had bone metastases. EX resulted in a significant reduction in physical fatigue (-5.3 [-10.0; -0.6], p=.027, ES=0.22) and improvement in HRQoL (+4.8 [2.2; 7.4], p=.0003, ES=0.33) compared to UC at 6 months (primary endpoint), as well as at 3 and 9 months. EX also improved physical fitness (+24.3 Watts, [15.5; 33.1], ES=0.42, at 6 months) and numerous relevant QLQ-C30 scales, including social functioning, pain, and dyspnoea. CONCLUSION This large multinational study demonstrates that supervised exercise improves fatigue, HRQoL, and other clinically relevant outcomes in patients with mBC. Based on these findings, supervised exercise should be recommended to patients with mBC.