Randomized Controlled Trial of Aerobic Exercise on Insulin and Insulin-like Growth Factors in Breast Cancer Survivors: The Yale Exercise and Survivorship Study

Department of Epidemiology and Public Health, Yale School of Medicine, P.O. Box 208034, New Haven, CT 06520-8034, USA.
Cancer Epidemiology Biomarkers & Prevention (Impact Factor: 4.13). 01/2009; 18(1):306-13. DOI: 10.1158/1055-9965.EPI-08-0531
Source: PubMed


High insulin and insulin-like growth factor-I (IGF-I) levels may be associated with an increased breast cancer risk and/or death. Given the need to identify modifiable factors that decrease insulin, IGF-I, and breast cancer risk and death, we investigated the effects of a 6-month randomized controlled aerobic exercise intervention versus usual care on fasting insulin, IGF-I, and its binding protein (IGFBP-3) in postmenopausal breast cancer survivors.
Seventy-five postmenopausal breast cancer survivors were identified from the Yale-New Haven Hospital Tumor Registry and randomly assigned to an exercise (n = 37) or usual care (n = 38) group. The exercise group participated in 150 minutes per week of moderate-intensity aerobic exercise. The usual care group was instructed to maintain their current physical activity level. A fasting blood sample was collected on each study participant at baseline and 6 months. Blood levels of insulin and IGF were measured with ELISA.
On average, exercisers increased aerobic exercise by 129 minutes per week compared with 45 minutes per week among usual care participants (P < 0.001). Women randomized to exercise experienced decreases in insulin, IGF-I, and IGFBP-3, whereas women randomized to usual care had increases in these hormones. Between-group differences in insulin, IGF-I, and IGFBP-3 were 20.7% (P = 0.089), 8.9% (P = 0.026), and 7.9% (P = 0.006), respectively.
Moderate-intensity aerobic exercise, such as brisk walking, decreases IGF-I and IGFBP-3. The exercise-induced decreases in IGF may mediate the observed association between higher levels of physical activity and improved survival in women diagnosed with breast cancer.

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Available from: Susan T Mayne, Oct 07, 2015
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    • "Of the four [21,23-25] studies reporting a high quality measure of body composition after exercise alone, two aerobic exercise studies (one controlled, one uncontrolled) reported statistically non-significant trends in LBM change [24,25], while separate aerobic [21] and resistance training [23] trials indicated a significant increase in LBM compared to control groups (+0.8 kg vs -0.8 kg, p = 0.047 & +0.88 kg vs +0.02 kg, P = 0.008, respectively). After further analysis, Irwin et al [36] found that exercisers aged <56 years had greater LBM gains than women >56 years and non-exercisers, and those taking AIs and exercising had greater LBM increases than those not taking AIs. "
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    ABSTRACT: Loss of lean body mass (LBM) is a common occurrence after treatment for breast cancer and is related to deleterious metabolic health outcomes [Clin Oncol, 22(4):281-288, 2010; Appl Physiol Nutr Metab, 34(5):950-956, 2009]. The aim of this research is to determine the effectiveness of long chain omega-3 fatty acids (LCn-3s) and exercise training alone, or in combination, in addressing LBM loss in breast cancer survivors.Methods/design: A total of 153 women who have completed treatment for breast cancer in the last 12 months, with a Body Mass Index (BMI) of 20 to 35kg/m2, will be randomly assigned to one of 3 groups: 3g/d LCn-3s (LC), a 12-week nutrition and exercise education program plus olive oil (P-LC) or the education program plus LCn-3s (E-LC). Participants randomised to the education groups will be blinded to treatment, and will receive either olive oil placebo (P) or LCn-3 provision, while the LC group will be open label. The education program includes nine 60-75min sessions over 12 weeks that will involve breast cancer specific healthy eating advice, plus a supervised exercise session run as a resistance exercise circuit. They will also be advised to conduct the resistance training and aerobic training 5 to 7 days per week collectively. Outcome measures will be taken at baseline, 12-weeks and 24-weeks. The primary outcome is % change in LBM as measured by the air displacement plethysmograhy. Secondary outcomes include quality of life (FACT-B + 4) and inflammation (C-Reactive protein: CRP). Additional measures taken will be erythrocyte fatty acid analysis, fatigue, physical activity, menopausal symptoms, dietary intake, joint pain and function indices. This research will provide the first insight into the efficacy of LCn-3s alone or in combination with exercise in breast cancer survivors with regards to LBM and quality of life. In addition, this study is designed to improve evidence-based dietetic practice, and how specific dietary prescription may link with appropriate exercise interventions.Trials registration: ACTRN12610001005044; and World Health Organisation Universal trial number: U1111-1116-8520.
    BMC Cancer 04/2014; 14(1):264. DOI:10.1186/1471-2407-14-264 · 3.36 Impact Factor
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    • "Not only has physical activity been associated with decreased breast cancer risk [17-19], it has also been shown to be beneficial for breast cancer survivors. For example, aerobic exercise has been found to improve cardiorespiratory function in survivors 6 months to 5 years post-treatment [12,13,20,21], which is particularly important for survivors who have had cardiac damage from chemotherapy. Resistance exercise has been found to increase muscle strength [7,14,22,23], which subsequently reduces injuries and improves balance. "
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    ABSTRACT: Metabolic syndrome (MetS) is increasingly present in breast cancer survivors, possibly worsened by cancer-related treatments, such as chemotherapy. MetS greatly increases risk of cardiovascular disease and diabetes, co-morbidities that could impair the survivorship experience, and possibly lead to cancer recurrence. Exercise has been shown to positively influence quality of life (QOL), physical function, muscular strength and endurance, reduce fatigue, and improve emotional well-being; however, the impact on MetS components (visceral adiposity, hyperglycemia, low serum high-density lipoprotein cholesterol, hypertriglyceridemia, and hypertension) remains largely unknown. In this trial, we aim to assess the effects of combined (aerobic and resistance) exercise on components of MetS, as well as on physical fitness and QOL, in breast cancer survivors soon after completing cancer-related treatments.Methods/design: This study is a prospective randomized controlled trial (RCT) investigating the effects of a 16-week supervised progressive aerobic and resistance exercise training intervention on MetS in 100 breast cancer survivors. Main inclusion criteria are histologically-confirmed breast cancer stage I-III, completion of chemotherapy and/or radiation within 6 months prior to initiation of the study, sedentary, and free from musculoskeletal disorders. The primary endpoint is MetS; secondary endpoints include: muscle strength, shoulder function, cardiorespiratory fitness, body composition, bone mineral density, and QOL. Participants randomized to the Exercise group participate in 3 supervised weekly exercise sessions for 16 weeks. Participants randomized to the Control group are offered the same intervention after the 16-week period of observation. This is the one of few RCTs examining the effects of exercise on MetS in breast cancer survivors. Results will contribute a better understanding of metabolic disease-related effects of resistance and aerobic exercise training and inform intervention programs that will optimally improve physiological and psychosocial health during cancer survivorship, and that are ultimately aimed at improving prognosis.Trial registration: NCT01140282; Registration: June 10, 2010.
    BMC Cancer 04/2014; 14(1):238. DOI:10.1186/1471-2407-14-238 · 3.36 Impact Factor
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    • "The biological mechanisms by which physical activity may modify cancer risk or disease progression, or improve symptom control, include changes in insulin-like growth factor (IGF) levels, immune regulation, sex and metabolic hormone levels, prostaglandin ratio and obesity [16,32-35]. More specific to lung cancer, physical activity improves pulmonary function and perfusion, [36] and it is hypothesised that physical activity may up-regulate antioxidants and free scavengers to help counteract the effects of cigarette smoke [37]. "
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    ABSTRACT: Background People with lung cancer have substantial symptom burden and more unmet needs than the general cancer population. Physical activity (PA) has been shown to positively influence quality of life (QOL), fatigue and daily functioning in the curative treatment of people with breast and colorectal cancers and lung diseases, as well as in palliative settings. A randomised controlled trial (RCT) is needed to determine if lung cancer patients benefit from structured PA intervention. The Physical Activity in Lung Cancer (PAL) trial is designed to evaluate the impact of a 2-month PA intervention on fatigue and QOL in patients with non-resectable lung cancer. Biological mechanisms will also be studied. Methods/design A multi-centre RCT with patients randomised to usual care or a 2-month PA programme, involving supervised PA sessions including a behavioural change component and home-based PA. QOL questionnaires, disease and functional status and body composition will be assessed at baseline, 2, 4 and 6 months follow-up. The primary endpoint is comparative levels of fatigue between the 2 arms. Secondary endpoints include: QOL, functional abilities and physical function. Exploratory endpoints include: anxiety, depression, distress, dyspnoea, PA behaviour, fitness, hospitalisations, survival, cytokines and insulin-like growth factor levels. Discussion This study will provide high-level evidence of the effect of PA programmes on cancer-related fatigue and QOL in patients with advanced lung cancer. If positive, the study has the potential to change care for people with cancer using a simple, inexpensive intervention to improve their QOL and help them maintain independent function for as long as possible. Trial registration Australian New Zealand Clinical Trials Registry No. ACTRN12609000971235
    BMC Cancer 12/2012; 12(1):572. DOI:10.1186/1471-2407-12-572 · 3.36 Impact Factor
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