Kristin L. Campbell

Effects of exercise on breast cancer patients and survivors: a systematic review and meta-analysis

Background: Physical exercise has been identified as a potential intervention to improve quality of life in women with breast cancer. We sought to summarize the available evidence concerning the effects of exercise on breast cancer patients and survivors. Methods: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, PsychINFO, CancerLit, PEDro and SportDiscus as well as conference proceedings, clinical practice guidelines and other unpublished literature resources. We included only randomized controlled trials that examined exercise interventions for breast cancer patients or survivors with quality of life, cardiorespiratory fitness or physical functioning as primary outcomes. We also extracted data on symptoms of fatigue, body composition and adverse effects. Results: Of 136 studies identified, 14 met all the inclusion criteria. Despite significant heterogeneity and relatively small samples, the point estimates in terms of the benefits of exercise for all outcomes were positive even when statistical significance was not achieved. Exercise led to statistically significant improvements in quality of life as assessed by the Functional Assessment of Cancer Therapy–General (weighted mean difference [WMD] 4.58, 95% confidence interval [CI] 0.35 to 8.80) and Functional Assessment of Cancer Therapy–Breast (WMD 6.62, 95% CI 1.21 to 12.03). Exercise also led to significant improvements in physical functioning and peak oxygen consumption and in reducing symptoms of fatigue. Interpretation: Exercise is an effective intervention to improve quality of life, cardiorespiratory fitness, physical functioning and fatigue in breast cancer patients and survivors. Larger trials that have a greater focus on study quality and adverse effects and that examine the long-term benefits of exercise are needed for this patient group.

Alberta Physical Activity and Breast Cancer Prevention Trial: Sex Hormone Changes in a Year-Long Exercise Intervention Among Postmenopausal Women

PURPOSE We examined how an aerobic exercise intervention influenced circulating estradiol, estrone, sex hormone-binding globulin (SHBG), androstenedione, and testosterone levels, which may be involved in the association between physical activity and breast cancer risk. METHODS A two-center, two-arm randomized controlled trial of exercise was conducted in 320 postmenopausal, sedentary women age 50 to 74 years. Participants were randomly assigned to a 1-year aerobic exercise intervention of 225 min/wk (n = 160) or to a control group who maintained their usual level of activity (n = 160). Baseline, 6-month, and 12-month assessments of estrone, estradiol, androstenedione, and testosterone were quantified by radioimmunoassay after extraction, and SHBG was quantified by an immunometric assay. Intent-to-treat analyses were performed using linear mixed models. RESULTS Blood data were available on 309 women (96.6%) at 12 months. Women in the intervention group exercised an average of 3.6 d/wk for 178 min/wk. At 12 months, statistically significant reductions in estradiol (treatment effect ratio [TER] = 0.93; 95% CI, 0.88 to 0.98) and free estradiol (TER = 0.91; 95% CI, 0.87 to 0.96) and increases in SHBG (TER = 1.04; 95% CI, 1.02 to 1.07) were observed in the exercise group compared with the control group. No significant differences in estrone, androstenedione, and testosterone levels were observed between exercisers and controls at 12 months. CONCLUSION This trial found that previously sedentary postmenopausal women can adhere to a moderate- to vigorous-intensity exercise program that results in changes in estradiol and SHBG concentrations that are consistent with a lower risk for postmenopausal breast cancer.

Effects of a caloric restriction weight loss diet and exercise on inflammatory biomarkers in overweight/obese postmenopausal women: a randomized controlled trial.

Obese and sedentary persons have increased risk for cancer; inflammation is a hypothesized mechanism. We examined the effects of a caloric restriction weight loss diet and exercise on inflammatory biomarkers in 439 women. Overweight and obese postmenopausal women were randomized to 1-year: caloric restriction diet (goal of 10% weight loss, N = 118), aerobic exercise (225 min/wk of moderate-to-vigorous activity, N = 117), combined diet + exercise (N = 117), or control (N = 87). Baseline and 1-year high-sensitivity C-reactive protein (hs-CRP), serum amyloid A (SAA), interleukin-6 (IL-6), leukocyte, and neutrophil levels were measured by investigators blind to group. Inflammatory biomarker changes were compared using generalized estimating equations. Models were adjusted for baseline body mass index (BMI), race/ethnicity, and age. Four hundred and thirty-eight (N = 1 in diet + exercise group was excluded) were analyzed. Relative to controls, hs-CRP decreased by geometric mean (95% confidence interval, P value): 0.92 mg/L (0.53-1.31, P < 0.001) in the diet and 0.87 mg/L (0.51-1.23, P < 0.0001) in the diet + exercise groups. IL-6 decreased by 0.34 pg/mL (0.13-0.55, P = 0.001) in the diet and 0.32 pg/mL (0.15-0.49, P < 0.001) in the diet + exercise groups. Neutrophil counts decreased by 0.31 × 10(9)/L (0.09-0.54, P = 0.006) in the diet and 0.30 × 10(9)/L (0.09-0.50, P = 0.005) in the diet + exercise groups. Diet and diet + exercise participants with 5% or more weight loss reduced inflammatory biomarkers (hs-CRP, SAA, and IL-6) compared with controls. The diet and diet + exercise groups reduced hs-CRP in all subgroups of baseline BMI, waist circumference, CRP level, and fasting glucose. Our findings indicate that a caloric restriction weight loss diet with or without exercise reduces biomarkers of inflammation in postmenopausal women, with potential clinical significance for cancer risk reduction.

A yearlong exercise intervention decreases CRP among obese postmenopausal women.

PURPOSE To investigate the effect of a yearlong moderate-intensity aerobic exercise intervention on C-reactive protein (CRP), serum amyloid A (SAA), and interleukin 6 (IL-6) among overweight or obese postmenopausal women. METHODS In a randomized controlled trial, 115 postmenopausal, overweight or obese, sedentary women, aged 50-75 yr were randomized to an aerobic exercise intervention of moderate-intensity (60%-75% observed maximal HR), for > or = 45 min x d(-1), 5 d x wk (n = 53), or to a 1-d x wk(-1) stretching control (n = 62), on an intent-to-treat basis. CRP, SAA, and IL-6 were measured at baseline, at 3 months, and at 12 months. RESULTS From baseline to 12 months, CRP decreased 10% in exercisers and increased 12% in controls (P = 0.01); no effects were observed for SAA and IL-6. Among participants at baseline who were obese (body mass index (BMI) > or = 30 kg x m(-2)) or had abdominal obesity (waist circumference (WC) > or = 88 cm), exercise resulted in a more pronounced reduction in CRP (BMI > or = 30 kg x m(-2), P = 0.002; WC > or = 88 cm, P < 0.0001), borderline for SAA (BMI > or = 30 kg x m(-2), P = 0.08; WC > or = 88 cm, P = 0.04); no intervention effects were observed among women who did not have these characteristics. Overall, weight loss was minimal in the exercise intervention ( approximately 1.8 kg). Linear trends were observed between CRP and 12-month changes in aerobic fitness (Ptrend = 0.006), exercise adherence (Ptrend = 0.004), percentage body fat (Ptrend = 0.002), body weight (Ptrend = 0.002), WC (Ptrend = 0.02), and intra-abdominal fat (Ptrend = 0.03). CONCLUSIONS A moderate-intensity exercise intervention reduced CRP for 12 months among women who were obese at baseline. These findings support the role of exercise in modulating inflammatory processes that are related to increased risk of chronic disease among obese women.

Weight Management and its Role in Breast Cancer Rehabilitation

Overweight and obesity are risk factors for postmenopausal breast cancer, and many women diagnosed with breast cancer, irrespective of menopausal status, gain weight after diagnosis. Weight management plays an important role in rehabilitation and recovery because obesity and/or weight gain may lead to poorer breast cancer prognosis, as well as prevalent comorbid conditions (eg, cardiovascular disease and diabetes), poorer surgical outcomes (eg, increased operating and recovery times, higher infection rates, and poorer healing), lymphedema, fatigue, functional decline, and poorer health and overall quality of life. Health care professionals should encourage weight management at all phases of the cancer care continuum as a means to potentially avoid adverse sequelae and late effects, as well as to improve overall health and possibly survival. Comprehensive approaches that involve dietary and behavior modification, and increased aerobic and strength training exercise have shown promise in either preventing weight gain or promoting weight loss, reducing biomarkers associated with inflammation and comorbidity, and improving lifestyle behaviors, functional status, and quality of life in this high‐risk patient population. Cancer 2012;.

Exercise and biomarkers for cancer prevention studies.

The International Agency for Research on Cancer estimates that 25% of cancer cases worldwide are caused by overweight or obesity and a sedentary lifestyle. These lifestyle patterns may increase cancer risk by several mechanisms including increased estrogens and testosterone, hyperinsulinemia and insulin resistance, increased inflammation, and depressed immune function. Several randomized clinical trials have shown that physical activity and diet interventions can change biomarkers of cancer risk. In a controlled physical activity trial, we found decreases in serum estrogen, testosterone, and insulin in overweight, sedentary postmenopausal women with a 1-y exercise program consisting of moderate-intensity aerobic exercise, 45 min/d, 5 d/wk. In another controlled trial in middle-aged to older persons, we found that a 1-y exercise intervention of 60 min/d, 6 d/wk, reduced colon crypt cell proliferation in men who adhered closely to the program. Only 1 trial, the Womens Health Initiative Dietary Modification Trial, has published results of a dietary intervention on breast cancer incidence and reported a statistically nonsignificant 9% reduction in invasive breast cancer incidence in postmenopausal women following a low-fat dietary pattern for 8-12 y. Other trials under way are testing effects of weight loss, physical activity, and dietary patterns on other cancer biomarkers. The NCI-funded Transdisciplinary Research on Energetics and Cancer centers are exploring novel research into mechanisms linking energy balance with cancer risk and prevention. The worldwide trends toward increasing overweight and obesity and decreasing physical activity may lead to an increased incidence of several cancers unless other means of risk reduction counteract these effects. Thus, adoption of lifestyle changes by individuals and populations may have a large impact on the future incidence of cancer.

Promoting Neuroplasticity for Motor Rehabilitation After Stroke: Considering the Effects of Aerobic Exercise and Genetic Variation on Brain-Derived Neurotrophic Factor

Recovery of motor function after stroke involves relearning motor skills and is mediated by neuroplasticity. Recent research has focused on developing rehabilitation strategies that facilitate such neuroplasticity to maximize functional outcome poststroke. Although many molecular signaling pathways are involved, brain-derived neurotrophic factor (BDNF) has emerged as a key facilitator of neuroplasticity involved in motor learning and rehabilitation after stroke. Thus, rehabilitation strategies that optimize BDNF effects on neuroplasticity may be especially effective for improving motor function poststroke. Two potential poststroke rehabilitation strategies that consider the importance of BDNF are the use of aerobic exercise to enhance brain function and the incorporation of genetic information to individualize therapy. Converging evidence demonstrates that aerobic exercise increases BDNF production and consequently enhances learning and memory processes. Nevertheless, a common genetic variant reduces activity-dependent secretion of the BDNF protein. Thus, BDNF gene variation may affect response to motor rehabilitation training and potentially modulate the effects of aerobic exercise on neuroplasticity. This perspective article discusses evidence that aerobic exercise promotes neuroplasticity by increasing BDNF production and considers how aerobic exercise may facilitate the acquisition and retention of motor skills for poststroke rehabilitation. Next, the impact of the BDNF gene val66met polymorphism on motor learning and response to rehabilitation is explored. It is concluded that the effects of aerobic exercise on BDNF and motor learning may be better exploited if aerobic exercise is paired more closely in time with motor training. Additionally, information about BDNF genotype could provide insight into the type and magnitude of effects that aerobic exercise may have across individuals and potentially help guide an individualized prescription of aerobic exercise to enhance motor rehabilitation poststroke.

Dietary weight loss and exercise interventions effects on quality of life in overweight/obese postmenopausal women: a randomized controlled trial

BackgroundAlthough lifestyle interventions targeting multiple lifestyle behaviors are more effective in preventing unhealthy weight gain and chronic diseases than intervening on a single behavior, few studies have compared individual and combined effects of diet and/or exercise interventions on health-related quality of life (HRQOL). In addition, the mechanisms of how these lifestyle interventions affect HRQOL are unknown. The primary aim of this study was to examine the individual and combined effects of dietary weight loss and/or exercise interventions on HRQOL and psychosocial factors (depression, anxiety, stress, social support). The secondary aim was to investigate predictors of changes in HRQOL.MethodsThis study was a randomized controlled trial. Overweight/obese postmenopausal women were randomly assigned to 12 months of dietary weight loss (n = 118), moderate-to-vigorous aerobic exercise (225 minutes/week, n = 117), combined diet and exercise (n = 117), or control (n = 87). Demographic, health and anthropometric information, aerobic fitness, HRQOL (SF-36), stress (Perceived Stress Scale), depression [Brief Symptom Inventory (BSI)-18], anxiety (BSI-18) and social support (Medical Outcome Study Social Support Survey) were assessed at baseline and 12 months. The 12-month changes in HRQOL and psychosocial factors were compared using analysis of covariance, adjusting for baseline scores. Multiple regression was used to assess predictors of changes in HRQOL.ResultsTwelve-month changes in HRQOL and psychosocial factors differed by intervention group. The combined diet + exercise group improved 4 aspects of HRQOL (physical functioning, role-physical, vitality, and mental health), and stress (p ≤ 0.01 vs. controls). The diet group increased vitality score (p < 0.01 vs. control), while HRQOL did not change differently in the exercise group compared with controls. However, regardless of intervention group, weight loss predicted increased physical functioning, role-physical, vitality, and mental health, while increased aerobic fitness predicted improved physical functioning. Positive changes in depression, stress, and social support were independently associated with increased HRQOL, after adjusting for changes in weight and aerobic fitness.ConclusionsA combined diet and exercise intervention has positive effects on HRQOL and psychological health, which may be greater than that from exercise or diet alone. Improvements in weight, aerobic fitness and psychosocial factors may mediate intervention effects on HRQOL.Trial RegistrationClinical Trials, ClinicalTrials.gov register, NCT00470119

Changes in insulin resistance indicators, IGFs, and adipokines in a year-long trial of aerobic exercise in postmenopausal women

Physical activity is a known modifiable lifestyle means for reducing postmenopausal breast cancer risk, but the biologic mechanisms are not well understood. Metabolic factors may be involved. In this study, we aimed to determine the effects of exercise on insulin resistance (IR) indicators, IGF1, and adipokines in postmenopausal women. The Alberta Physical Activity and Breast Cancer Prevention Trial was a two-armed randomized controlled trial in postmenopausal, inactive, cancer-free women. A year-long aerobic exercise intervention of 225 min/week (n=160) was compared with a control group asked to maintain usual activity levels (n=160). Baseline, 6- and 12-month serum levels of insulin, glucose, IGF1, IGF-binding protein 3 (IGFBP3), adiponectin, and leptin were assayed, and after data collection, homeostasis model assessment of IR (HOMA-IR) scores were calculated. Intention-to-treat analyses were performed using linear mixed models. The treatment effect ratio (TER) of exercisers to controls was calculated. Data were available on 308 (96.3%) women at 6 months and 310 (96.9%) women at 12 months. Across the study period, statistically significant reductions in insulin (TER=0.87, 95% confidence interval (95% CI)=0.81–0.93), HOMA-IR (TER=0.86, 95% CI=0.80–0.93), and leptin (TER=0.82, 95% CI=0.78–0.87), and an increase in the adiponectin/leptin ratio (TER=1.21, 95% CI=1.13–1.28) were observed in the exercise group compared with the control group. No significant differences were observed for glucose, IGF1, IGFBP3, adiponectin or the IGF1/IGFBP3 ratio. Previously inactive postmenopausal women who engaged in a moderate-to-vigorous intensity exercise program experienced changes in insulin, HOMA-IR, leptin, and adiponectin/leptin that might decrease the risk for postmenopausal breast cancer.

Adiposity changes after a 1-year aerobic exercise intervention among postmenopausal women: a randomized controlled trial

Objective:We examined the effects of an aerobic exercise intervention on adiposity outcomes that may be involved in the association between physical activity and breast cancer risk.Design:This study was a two-centre, two-armed, randomized controlled trial. The 1-year-long exercise intervention included 45 min of moderate-to-vigorous aerobic exercise five times per week, with at least three of the sessions being facility based. The control group was asked not to change their activity and both groups were asked not to change their diet.Subjects:A total of 320 postmenopausal, sedentary, normal weight-to-obese women aged 50–74 years who were cancer-free, nondiabetic and nonhormone replacement therapy users were included in this study.Measurements:Anthropometric measurements of height, weight and waist and hip circumferences; dual energy X-ray absorptiometry measurements of total body fat; and computerized tomography measurements of abdominal adiposity were carried out.Results:Women in the exercise group exercised a mean of 3.6 days (s.d.=1.3) per week and 178.5 min (s.d.=76.1) per week. Changes in all measures of adiposity favored exercisers relative to controls (P<0.001). The mean difference between groups was: −1.8 kg for body weight; −2.0 kg for total body fat; −14.9 cm2 for intra-abdominal fat area; and −24.1 cm2 for subcutaneous abdominal fat area. A linear trend of greater body fat loss with increasing volume of exercise was also observed.Conclusion:A 1-year aerobic exercise program consistent with current public health guidelines resulted in reduced adiposity levels in previously sedentary postmenopausal women at higher risk of breast cancer.