Background Physical activity may provide benefits for breast cancer survivors in part by reducing systemic inflammation. Physical activity behavior change studies are a type of implementation research in which exercise efficacy information is translated into a “real world” setting, allowing determination of whether physical activity changes are sufficient to improve health outcomes. We hypothesized that breast cancer survivors (BCS) who undertook a physical activity behavior change intervention would have less systemic inflammation and improved cardiorespiratory fitness, muscle strength, body composition, fatigue, and sleep as compared with BCS receiving usual care. The goal of this pilot study was to determine the magnitude and direction of intervention effect sizes for inflammatory related serum markers and relevant health outcomes. Methods This randomized controlled trial enrolled 28 Stage I, II, or IIIA BCS who were post-primary treatment and were not regular exercisers. These women were assigned to either a 3-month physical activity behavior change intervention group (ING) or usual care group (UCG). Intervention included supervised aerobic (150 weekly minutes, moderate-intensity) and resistance (two sessions per week) exercise that gradually tapered to home-based exercise. At baseline and after 3 months, health outcomes and serum concentrations of interleukin (IL)-1 beta, IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-alpha, leptin, and adiponectin were measured. Results Cardiorespiratory fitness significantly improved in the ING versus UCG (between group difference=3.8 ml/kg/min; d=1.1; P=0.015). Self-reported sleep latency was significantly reduced in the ING versus UCG (between group difference=−0.5; d=−1.2; P=0.02) as was serum leptin (between group difference=−9.0 ng/ml; d=−1.0; P=0.031). Small to medium non-significant negative effect sizes were noted for IL-10 and TNF-alpha and ratios of IL-6:IL-10, IL-8:IL10, and TNF-alpha:IL-10, with non-significant positive effect sizes noted for IL-6 and high molecular weight adiponectin. Conclusions Physical activity behavior change interventions in BCS can achieve large effect size changes for several health outcomes. Although effect sizes for inflammatory markers were often small and not significant, changes were in the hypothesized direction for all except IL-6 and IL-10. These preliminary data support larger trials that would more fully examine potential inflammatory changes that accompany physical activity behavior change interventions.

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.

Although genetic risk factors for influenza infection have not yet been defined in people, differences in genetic background and related variation in the response to infection, as well as viral virulence, are all likely to influence both the likelihood of infection and disease severity. However, apart from characterization of viral binding sites in avian and mammalian hosts, relatively little investigation has focused on host genetic determinants of susceptibility or resistance to infection, or the severity of the associated disease in humans or other species. Similarly, the role of genetic background in the generation of an efficacious immune response to either infection or vaccination has not been extensively evaluated. However, genetic influences on susceptibility and resistance to numerous infectious agents and on the resultant host inflammatory and immune responses are well established in both humans and other animals. Mouse-adapted strains of human influenza viruses and the use of inbred strains of laboratory mice have supported extensive characterization of the pathogenesis and immunology of influenza virus infections. Like individual humans, inbred strains of mice vary in their reactions to influenza infection, particularly with regard to the inflammatory response and disease severity, supporting the potential use of these mice as a valuable surrogate for human genetic variation. Relying heavily on what we have learned from mice, this overview summarizes existing animal, human and epidemiologic data suggestive of host genetic influences on influenza infection.

Objective To improve mechanistic understanding, this pilot randomized controlled trial examined mediators of an exercise intervention effects on sleep in breast cancer survivors (BCS). Methods Forty-six postmenopausal BCS (≤ Stage II, off primary treatment) were randomized to a 3-month exercise intervention or control group. Intervention included 160 minutes/week of moderate intensity aerobic walking, twice weekly resistance training (resistance bands), and six discussion groups (to improve adherence). Blinded assessments at baseline and post-intervention included sleep disturbance (PSQI and PROMIS®), objective sleep quality (accelerometer), serum cytokines, accelerometer physical activity, cardiorespiratory fitness, body composition, fatigue, and psychosocial factors. Mediation was tested using Freedman-Schatzkin difference-in-coefficients tests. Results When compared with control, the intervention group demonstrated a significant increase in PSQI sleep duration (i.e., fewer hours of sleep/night) (d=0.73, p=.03). Medium to large but non-significant standardized effect sizes were noted for PSQI daytime somnolence (d=-0.63, p=.05) and accelerometer latency (d=-0.49, p=.14). No statistically significant mediators were detected for PSQI sleep duration score or accelerometer latency. Daytime somnolence was mediated by tumor necrosis factor (TNF)-alpha (mediated 23% of intervention effect, p<.05), interleukin (IL)-6: IL-10 (16%, p<.01), IL-8:IL-10 (26%, p<.01), and fatigue (38%, p<.05). Mediating or enhancing relationships for several of the sleep outcomes were noted for accelerometer physical activity, PROMIS® fatigue, exercise social support, and/or physical activity enjoyment. Conclusions Inflammation and psychosocial factors may mediate or enhance sleep response to our exercise intervention. Further study is warranted to confirm our results and translate our findings into more effective interventions aimed at improving sleep quality in BCS.

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