Exercise training, circulating cytokine levels and immune function in cancer survivors: A meta-analysis.

BACKGROUND: Anti-cancer therapies lead to chronic non-resolving inflammation and reduced immune function. One potential therapy is exercise training, but the effectiveness of these interventions to improve immune-related outcomes, the gaps in the literature, and recommendations to progress the field need to be determined. OBJECTIVES: (1) to conduct separate meta-analyses in cancer survivors to determine the effects of exercise training on pro- and anti-inflammatory markers, and immune cell proportions and function; and (2) to perform subgroup analyses to determine whether exercise modality, cancer type, and specific markers help to explain heterogeneity in each meta-analysis. DATA SOURCES: Electronic databases (PubMed/MEDLINE, EMBASE, CENTRAL, and CINAHL) from inception to March 2018. The reference lists of eligible articles and relevant reviews were also checked. STUDY SELECTION: Inclusion criteria were adult cancer survivors from randomized controlled trials performing structured exercise intervention (aerobic, resistance or combined training or Tai Chi/yoga) compared to usual care control group and included pro-inflammatory, anti-inflammatory, and/or immune cell outcomes. APPRAISAL AND SYNTHESIS METHODS: A total of 5349 potentially eligible articles were identified, of which 26 articles (27 trials) met the inclusion criteria. Effect sizes were calculated as standardized mean differences (SMD), where <0.2 was defined as trivial, 0.2-0.3 as small, 0.4-0.8 as moderate, and >0.8 as a large effect. RESULTS: Exercise training decreased pro-inflammatory markers (SMD: -0.2, 95% CI: -0.4, -0.1, p < 0.001). Sub-group analysis for the pro-inflammatory markers indicated that combined aerobic and resistance training had the greatest effect (SMD: -0.3, 95% CI: -0.5, -1.9, p < 0.001), that prostate (SMD: -0.5, 95% CI: -0.8, 0.1, p = 0.004) and breast cancer populations were most responsive (SMD: -0.2, 95% CI: -0.3, -0.1, p = 0.001), and that C-reactive protein (SMD: -0.5, 95% CI: -0.9, -0.06, p = 0.025) and tumor necrosis factor (SMD: -0.3, 95% CI: -0.5, -0.06, p = 0.004) were the most sensitive to change. Exercise training tended to decrease anti-inflammatory markers (p = 0.072) but had no effect on natural killer or natural killer T cell proportions or cytotoxic activity. CONCLUSIONS: Exercise training reduces pro-inflammatory markers in cancer survivors, with the strongest evidence for combined training and for prostate and breast cancer survivors. Further research is warranted to determine if these changes are clinically relevant or are associated with improvements in symptoms. To strengthen future research, focusing on novel immune populations that include functional parameters and standardized reporting of key immune outcomes is recommended.

Effectiveness of home-based exercise in breast cancer survivors: a randomized clinical trial.

BACKGROUND: Breast cancer patients are recommended to engage in regular exercise. In developing countries, where there is a lack of facilities to offer specialized, supervised exercise for this population, regularly exercising might be a challenge. We aimed to evaluate the effectiveness of a home-based intervention in this population. METHODS: Breast cancer survivors were randomly assigned to either the home-based exercise program or the usual care group. Exercise intervention included walking, balance, and stretch exercises, along with weekly follow-up telephone calls. Quality of life (QOL) was evaluated using EORTC QLQ-C30 and EORTC QLQ-BR23 questionnaires and the predicted VO2 peak was measured using the Ebbeling submaximal treadmill test. RESULTS: Eighty-nine patients were enrolled in the study. Reported minutes of exercise gradually increased from 40.7 min per week in week 1 to 116.9 min per week in week 12. This intervention improved global QOL (P = 0.001), social functioning (P = 0.04), and the predicted VO2 peak (P = 0.01). CONCLUSION: This home-based exercise regime effectively increased quality of life and physical activity levels. TRIAL REGISTRY: Iranian Registry of Clinical Trials identifier: IRCT20140810018746N1, prospectively registered 08/01/2018, https://en.irct.ir/trial/27959 .

Exercise-induced modulation of monocytes in breast cancer survivors.

BACKGROUND: Exercise training reduces inflammation in breast cancer survivors; however, the mechanism is not fully understood. OBJECTIVES: The effects of acute and chronic exercise on monocyte toll-like receptor (TLR2 and 4) expression and intracellular cytokine production were examined in sedentary breast cancer survivors. METHODS: Eleven women with stage I, II, or III breast cancer within one year of treatment completion performed an acute, intermittent aerobic exercise trial. Blood samples were obtained before, immediately, and 1 h after a 45-min acute exercise trial that was performed before and after 16 weeks of combined aerobic and resistance. LPS-stimulated intracellular IL-1ß, TNF, and IL-6 production, and TLR2 and TLR4 expression were evaluated in CD14+CD16- and CD14+CD16+ monocytes using flow cytometry. RESULTS: Exercise training decreased IL-1ß+CD14+CD16- proportion (24.6%, p=0.016), IL-1ß+CD14+CD16- mean fluorescence intensity (MFI) (-9989, p=0.014), IL-1ß+CD14+CD16+ MFI (-11101, p=0.02), and IL-6+CD14+CD16- proportion (16.9%, P=0.04). TLR2 and TLR4 expression did not change following exercise training but decreased 1 h after acute exercise in CD14+CD16- (-63, p=0.002) and CD14+CD16+ (-18, p=0.006) monocytes, respectively. Immediately after the acute exercise, both monocyte subgroup cell concentration increased, with CD14+CD16+ concentrations being decreased at 1 h post without changes in intracellular cytokine production. CONCLUSIONS: Exercise training reduced monocyte intracellular pro-inflammatory cytokine production, especially IL-1ß, although these markers did not change acutely. While acute exercise downregulated the expression of TLR2 and TLR4 on monocytes, this was not sustained over the course of training. These results suggest that the anti-inflammatory effect of combined aerobic and resistance exercise training in breast cancer survivors may be, in part, due to reducing resting monocyte pro-inflammatory cytokine production.

Effect of 6 months of aerobic training on adipokines as breast cancer risk factors in postmenopausal women: A randomized controlled trial.

PURPOSE: Physical activity has been introduced as an inexpensive and effective behavior to reduce postmenopausal breast cancer risk. Decreased concentrations of adipokines such as leptin and resistin may be a possible mechanism. This study aimed to investigate the effects of 6 months of aerobic training on leptin and resistin levels in postmenopausal women. MATERIALS AND METHODS: The study participants were 50-74 years old, sedentary and postmenopausal women. Forty-one women met the inclusion criteria and were randomly assigned to the training (n = 22) or the control group (n = 19). Participants in intervention group engaged in a moderate supervised aerobic training, 3 days per week for 6 months, while controls were asked not to change their physical activity levels for the duration of the trial. Plasma concentrations of leptin and resistin, aerobic fitness, and anthropometric measures were assessed at baseline and after 6 months. RESULTS: Twenty-seven out of 41 participants completed the study. Plasma leptin decreased by 0.6% in exercisers and increased by 8.2% in controls; however, the exercise effect was not statistically significant. Plasma concentrations of resistin also decreased by 16.1% and 15.1% in exercise and control group, respectively. Aerobic fitness increased, and body mass index (BMI) decreased significantly in the intervention group. CONCLUSIONS: The exercise intervention did not have a statistically significant impact on the concentrations of the adipokines in question; however, this long-term aerobic training reduced BMI and body fat percentage and enhanced aerobic fitness. Thus, exercise programs can be considered as an effective behavioral modification in breast cancer prevention.