Joris Mallard, Elyse Hucteau, Roland Schott, Xavier Pivot, Allan F. Pagano, Thomas J. Hureau
Int. J. Cancer. 2025;1–12. wileyonlinelibrary.com/journal/ijc
Summary
This cohort study investigated the development of cancer-related fatigue (CRF) in 100 women undergoing chemotherapy for early breast cancer. CRF, a pervasive and multifactorial symptom, was assessed alongside exercise capacity, muscle force, neuromuscular fatigue, and physical activity at three time points: before chemotherapy, at 8 weeks, and after completion.
Seven distinct fatigue trajectories were identified, with three patterns comprising 78% of patients: never fatigued (34%), fatigued at both 8 weeks and post-treatment (25%), and fatigued only after chemotherapy (19%). By treatment completion, 54% of participants met the threshold for clinically significant fatigue.
Compared to non-fatigued patients, those experiencing CRF showed reduced exercise capacity, evidenced by greater declines in 6-minute walk test (6-MWT) distance, as well as higher neuromuscular fatigue in knee extensors and handgrip muscles. Notably, a >2.6% reduction in 6-MWT distance at 8 weeks and >7% reduction post-chemotherapy predicted risk for CRF. Physical activity levels were consistently lower among fatigued patients, though muscle mass changes were similar between groups.
Regression analyses demonstrated that changes in knee extensor neuromuscular fatigue, 6-MWT performance, knee extensor force, and physical activity collectively explained 39% of the variance in CRF progression. These findings highlight the interplay between physiological deconditioning and CRF development during treatment.
Clinical Implications
This study underscores the heterogeneity of CRF trajectories and the need for proactive monitoring throughout chemotherapy. Regular assessment of exercise capacity and neuromuscular fatigue, in addition to subjective fatigue scores, can help identify high-risk patients early.
The results reinforce exercise training as the most effective non-pharmacological intervention. Specifically, programs combining aerobic and resistance exercise to target both cardiovascular fitness and neuromuscular strength may mitigate CRF and preserve quality of life. Importantly, interventions should begin at chemotherapy initiation rather than after treatment completion, when fatigue is already entrenched.
Focused Takeaway for Clinicians
For breast cancer patients receiving chemotherapy, declines in 6-MWT distance and increased neuromuscular fatigue are strong markers of CRF risk. Routine functional assessments during treatment should guide timely referral to structured exercise programs, with emphasis on aerobic and resistance training. Early, tailored interventions can reduce fatigue burden, enhance treatment adherence, and improve survivorship outcomes.
