Biobehavioral Factors Mediate Exercise Effects on Fatigue in Breast Cancer Survivors

Abstract

Purpose Examine mediators of fatigue response to an exercise intervention for breast cancer survivors (BCS) in a pilot randomized controlled trial. Methods Postmenopausal BCS (n=46; ≤ Stage II), off primary treatment, and reporting fatigue and/or sleep dysfunction were randomized to a 3-month exercise intervention (160 minutes/week of moderate intensity aerobic walking, twice weekly resistance training with resistance bands) or control group. Six discussion group sessions provided behavioral support to improve adherence. Fatigue, serum cytokines, accelerometer physical activity, cardiorespiratory fitness, sleep dysfunction, and psychosocial factors were assessed at baseline and 3 months. Results Exercise intervention effect sizes for fatigue were: fatigue intensity d=0.30 (p=.34), interference d=−0.38 (p=.22), and general fatigue d=−0.49 (p=.13). Using Freedman-Schatzkin difference-in-coefficients tests, increase in fatigue intensity was significantly mediated by interleukin (IL)-6 (82%), IL-10 (94%), IL-6:IL-10 (49%), and tumor necrosis factor (TNF)-alpha:IL-10 (78%) with reduced sleep dysfunction increasing the relationship between intervention and fatigue intensity rather than mediating intervention effects (−88%). Decrease in fatigue interference was mediated by sleep dysfunction (35%) while IL-10 and pro:anti-inflammatory cytokine ratios increased the relationship between intervention and interference (−25% to −40%). The reduction in general fatigue was significantly mediated by minutes of physical activity (76%), sleep dysfunction (45%), and physical activity enjoyment (40%) with IL-10 (−40%) and IL-6:IL-10 (−11%) increasing the intervention-fatigue relationship. In the intervention group, higher baseline fatigue, anxiety, depression, and perceived exercise barriers interference predicted a greater decline in fatigue interference and/or general fatigue during the intervention. Conclusions Biobehavioral factors mediated and enhanced intervention effects on fatigue while psychosocial factors predicted fatigue response. Further study is warranted to confirm our results and improve understanding of relationships that mediate and strengthen the intervention-fatigue association.

Mediators of Exercise Effects on HRQoL in Cancer Survivors after Chemotherapy

“…The lack of mediating effect of improved cardiorespiratory fitness on general fatigue is in line with previous findings in prostate (8) and breast cancer survivors (30). This may be explained by the fact that general fatigue does not only include physical aspects, but also mental aspects, which are perhaps more likely influenced by concepts other than or additional to cardiorespiratory fitness.…”

“…This may be explained by the fact that general fatigue does not only include physical aspects, but also mental aspects, which are perhaps more likely influenced by concepts other than or additional to cardiorespiratory fitness. It is possible that psychological factors such as depression and anxiety may mediate exercise effects on general fatigue (30). Furthermore, exercise effects on fatigue could also be mediated by biological factors (e.g., improved body composition, and increased pro-inflammatory cytokines (31), or other psychosocial factors, such as reduced sleep quality, mastery, and self-efficacy (10, 30).…”

Inflammation and psychosocial factors mediate exercise effects on sleep quality in breast cancer survivors: pilot randomized controlled trial

“…This randomized controlled trial has been described in a previous publication reporting mediators of fatigue with a brief summary provided here. A 3‐month exercise intervention was compared with the control group; outcomes were obtained at baseline (pre‐intervention; M0) and 3 months (post‐intervention; M3) with a small monetary incentive paid to the participants after completion of each assessment.…”

“…Individuals were also excluded if they anticipated any of the following during study participation: (a) moving residence outside local area, (b) changes in usual medications, (c) elective surgery, or (d) travel outside local area during the first 4 weeks of the intervention or for >1 week during the last 8 weeks of the intervention. Participants with health conditions that increased exercise risk, prevented ability to comply with study activities, or significantly altered systemic inflammation were excluded .…”

Lower rate-pressure product during submaximal walking: a link to fatigue improvement following a physical activity intervention among breast cancer survivors

“…Due to the increased risk of occult cardiovascular disease and cardiomyopathies in BCS, it is of clinical interest to evaluate RPP in this population. Additionally, given the inconsistent link between aerobic fitness and fatigue in cancer survivors [19–22], research exploring the association between other cardiovascular fitness indicators and fatigue is needed.…”