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Biobehavioral factors mediate exercise effects on fatigue in breast cancer survivors.

ABSTRACT: This study aimed to examine mediators of fatigue response to an exercise intervention for breast cancer survivors in a pilot randomized controlled trial.Postmenopausal breast cancer survivors (n = 46; ?stage 2), off primary treatment, and reporting fatigue and/or sleep dysfunction were randomized to a 3-month exercise intervention (160 min·wk 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.The exercise intervention effect sizes for fatigue were as follows: fatigue intensity d = 0.30 (P = 0.34), interference d = -0.38 (P = 0.22), and general fatigue d = -0.49 (P = 0.13). Using the Freedman-Schatzkin difference-in-coefficients tests, increase in fatigue intensity was significantly mediated by interleukin 6 (IL-6) (82%), IL-10 (94%), IL-6/IL-10 (49%), and tumor necrosis factor-? (TNF-?):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%), whereas 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 barrier interference predicted a greater decline in fatigue interference and/or general fatigue during the intervention.Biobehavioral factors mediated and enhanced intervention effects on fatigue, whereas psychosocial factors predicted fatigue response. Further study is warranted to confirm our results and to improve understanding of relationships that mediate and strengthen the intervention-fatigue association.

SUBMITTER: Rogers LQ

PROVIDER: S-EPMC4435796 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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Biobehavioral factors mediate exercise effects on fatigue in breast cancer survivors.

Rogers Laura Q LQ Vicari Sandra S Trammell Rita R Hopkins-Price Patricia P Fogleman Amanda A Spenner Allison A Rao Krishna K Courneya Kerry S KS Hoelzer Karen S KS Robbs Randall R Verhulst Steven S

Medicine and science in sports and exercise 20140601 6

<h4>Purpose</h4>This study aimed to examine mediators of fatigue response to an exercise intervention for breast cancer survivors in a pilot randomized controlled trial.<h4>Methods</h4>Postmenopausal breast cancer survivors (n = 46; ≤stage 2), off primary treatment, and reporting fatigue and/or sleep dysfunction were randomized to a 3-month exercise intervention (160 min·wk of moderate-intensity aerobic walking, twice weekly resistance training with resistance bands) or control group. Six discus ...[more]

PMID: 24212124

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Project description:PurposeThe randomized controlled OptiTrain trial showed beneficial effects on fatigue after a 16-wk exercise intervention in patients with breast cancer undergoing adjuvant chemotherapy. We hypothesize that exercise alters systemic inflammation and that this partially mediates the beneficial effects of exercise on fatigue.MethodsTwo hundred and forty women scheduled for chemotherapy were randomized to 16 wk of resistance and high-intensity interval training (RT-HIIT), moderate-intensity aerobic and high-intensity interval training (AT-HIIT), or usual care (UC). In the current mechanistic analyses, we included all participants with >60% attendance and a random selection of controls (RT-HIIT = 30, AT-HIIT = 27, UC = 29). Fatigue (Piper Fatigue Scale) and 92 markers (e.g., interleukin-6 [IL-6] and tumor necrosis factor ? [TNF-?]) were assessed at baseline and postintervention. Mediation analyses were conducted to explore whether changes in inflammation markers mediated the effect of exercise on fatigue.ResultsOverall, chemotherapy led to an increase in inflammation. The increases in IL-6 (pleiotropic cytokine) and CD8a (T-cell surface glycoprotein) were however significantly less pronounced after RT-HIIT compared with UC (-0.47, 95% confidence interval = -0.87 to -0.07, and -0.28, 95% confidence interval = -0.57 to 0.004, respectively). Changes in IL-6 and CD8a significantly mediated the exercise effects on both general and physical fatigue by 32.0% and 27.7%, and 31.2% and 26.4%, respectively. No significant between-group differences in inflammatory markers at 16 wk were found between AT-HIIT and UC.ConclusionsThis study is the first showing that supervised RT-HIIT partially counteracted the increase in inflammation during chemotherapy, i.e., IL-6 and soluble CD8a, which resulted in lower fatigue levels postintervention. Exercise, including both resistance and high-intensity aerobic training, might be put forward as an effective treatment to reduce chemotherapy-induced inflammation and subsequent fatigue.

Project description:Following therapy, breast cancer survivors (BCS) have an increased risk of infections because of age and cancer dysregulation of inflammation and neutrophil functions. Neutrophil functions may be improved by exercise training, although limited data exist on exercise and neutrophil functions in BCS.Sixteen BCS [mean age: 56 (SD 11) years old] completed 16 weeks of community-based exercise training and a 45-minute acute bout of cycling before (Base) and after (Final) the exercise training program. Exercise training consisted of 3 x 40 - 60 minute mixed mode aerobic exercises, comprising 10 - 30 minutes aerobic and 30 minutes resistance training. At Base and Final, we took BCS blood samples before (PRE), immediately after (POST), and 1 hour after (1Hr) acute exercise to determine neutrophil counts, phenotype, bacterial killing, IL-6, and IL-8 levels. Eleven healthy, age- and physical activity levels-matched women (Control) completed the acute bout of exercise once as a healthy response reference. Resting Responses. BCS and Controls had similar Base PRE absolute neutrophil counts [mean (SD): 3.3 (1.9) v 3.1 (1.2) x 109/L, p=0.801], but BCS had lower bacterial phagocytosis [3991 (1233) v 4881 (417) MFI, p=0.035] and higher oxidative killing [6254 (1434) v 4709 (1220) MFI, p=0.005], lower CD16 [4159 (1785) v 7018 (1240) MFI, p<0.001], lower CXCR2 [4878 (1796) v 6330 (1299) MFI, p=0.032] and higher TLR2 [98 (32) v 72 (17) MFI, p=0.022] expression, while IL-6 [7.4 (5.4) v 4.0 (2.7) pg/mL, p=0.079] levels were marginally higher and IL-8 [6.0 (4.7) v 7.9 (5.0) pg/mL, p=0.316] levels similar. After 16 weeks of training, compared to Controls, BCS Final PRE phagocytosis [4510 (738) v 4881 (417) MFI, p=0.146] and TLR2 expression [114 (92) v 72 (17) MFI, p=0.148] were no longer different. Acute Exercise Responses. As compared to Controls, at Base, BCS phagocytic Pre-Post response was lower [mean difference, % (SD): 12% (26%), p=0.042], CD16 Pre-Post response was lower [12% (21%), p=0.016] while CD16 Pre-1Hr response was higher [13% (25%), p=0.022], TLR2 Pre-Post response was higher [15% (4%) p=0.002], while IL-8 Pre-Post response was higher [99% (48%), p=0.049]. As compared to Controls, following 16 weeks of training BCS phagocytic Pre-Post response [5% (5%), p=0.418], CD16 Pre-1Hr response [7% (7%), p=0.294], TLR2 Pre-Post response [6% (4%), p=0.092], and IL-8 Pre-Post response [1% (9%), p=0.087] were no longer different. Following cancer therapy, BCS may have impaired neutrophil functions in response to an acute bout of exercise that are partially restored by 16 weeks of exercise training. The improved phagocytosis of bacteria in BCS may represent an exercise-induced intrinsic improvement in neutrophil functions consistent with a reduced risk of infectious disease.Clinical trial registrationClinicalTrials.gov, identifier NCT03760536.

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Biobehavioral factors mediate exercise effects on fatigue in breast cancer survivors.

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Biobehavioral factors mediate exercise effects on fatigue in breast cancer survivors.

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