Breast Cancer and Exercise Trial in Alberta

Study Overview
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Brief Summary
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The Breast Cancer and Exercise Trial (BETA Trial) is a randomized controlled trial aimed at understanding what dose (or volume) of exercise will best reduce the risk for breast cancer, particularly among women who are between the ages of 50-74. The primary aim is to compare the effects of a high versus moderate volume exercise intervention on specific biological intermediate endpoints for breast cancer in a group of previously inactive postmenopausal women

Detailed Description
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Overview The proposed project is an evolution from a previous randomized controlled intervention trial conducted by the applicants known as the Alberta Physical Activity and Breast Cancer Prevention (ALPHA) Trial that examined how a one-year aerobic exercise intervention, as compared to a usual sedentary lifestyle, influenced specific hypothesized biologic mechanisms in the association between physical activity and breast cancer risk. In the proposed project, we plan to extend this research to examine how a one-year high versus moderate volume aerobic exercise intervention influences established and novel biologic mechanisms thought to influence breast cancer risk. We are specifically interested in studying what dose of exercise is required to influence the biologic mechanisms involved in breast cancer etiology. Rationale and Significance Inadequate physical activity, high total caloric intake, and obesity, central adiposity and weight gain throughout lifetime are all clearly associated with increased postmenopausal breast cancer risk and are some of the few risk factors amenable to intervention. Over one third of breast cancer can be attributed to these three risk factors. The exact dose and type of physical activity required for breast cancer risk reduction, however, are unknown. No trials have been conducted that have systematically examined how different volumes of activity influence mechanisms in breast cancer etiology. Study Aims The primary aim is to compare the effects of a high versus moderate volume exercise intervention on specific hormonal and biological intermediate endpoints for breast cancer in a group of previously sedentary postmenopausal women. The primary objectives will examine the effects of the interventions on measures of adiposity, insulin resistance, sex hormone levels, markers of obesity and inflammation and serum vitamin D. The secondary aim is to evaluate the impact of the high versus moderate exercise interventions among postmenopausal, sedentary women on psychosocial factors. The secondary objectives will compare the effects of the exercise interventions on quality of life and perceived stress among the participants. Adherence to the exercise intervention at 12 and maintenance of exercise at 24 months will also be assessed. Research Plan A two-centered, two-armed randomized controlled trial is proposed. In total, 330 postmenopausal, sedentary women aged 50-74 years will be recruited from the screening programs and through media campaigns. Strict eligibility criteria will be applied to ensure that women enrolled in the study can be expected to have a change in breast cancer risk over the one-year long intervention. Randomization will be stratified on centre (Calgary or Edmonton) and on body mass index (< or ≥27.5). The intervention arm will undertake aerobic exercise sessions of 300 mins/week for 12 months. The control arm will be asked to undertake 150 mins/week for 12 months. Baseline and 12-month measurements of adiposity (done by computerized tomography and dual energy X-ray absorbitometry scans), fitness, diet, physical activity, quality of life and stress, determinants of exercise adherence and medical, health and demographic characteristics will be made. Bloods, drawn at baseline, six and 12 months, will be assayed to measure estrone, estradiol, testosterone, androstenedione, insulin, glucose, adiponectin, leptin, interleukin-6, tumour necrosing factor-alpha, C-reactive protein and serum hydroxyvitamin D. One year after completion of the study, maintenance of physical and dietary habits will be measured. Intent-to-treat analysis will be used with a Laird-Ware mixed effects model to compare the changes from the baseline to 12-month follow-up. These data will be of direct relevance for effectiveness trials of exercise and diet for breast cancer prevention and for refinement of physical activity guidelines.

Official Title
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Breast Cancer and Exercise Trial in Alberta: The BETA Trial

Conditions
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Breast Neoplasms

Intervention / Treatment
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* Other: Moderate Volume
* Other: High Volume


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: 50- 74 years, postmenopausal women No previous cancer diagnosis Physically fit to undertake exercise program Pass the Physical Activity Readiness Medical Exam,acceptable heart and lung function during a sub-maximal treadmill test Body mass index : 22 - 40 Non-users of exogenous hormones or drugs related to estrogen metabolism, breast tissue growth Non-Smoker and non-excessive alcohol drinkers Residents of Calgary and Edmonton able to attend fitness facility regularly. Exclusion Criteria: < 50 years of age Diabetes Deemed too fit or too unfit on sub-maximal treadmill test Non English Speaking > 4 consecutive weeks absence during the intervention period

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 74 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Phase 3 - To compare the effects of a high versus moderate volume exercise intervention on specific biological intermediate endpoints for breast cancer in a group of previously inactive postmenopausal women.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: High Volume<br>Participate in one year of high volume (300 minutes per week) aerobic exercise with free provision of a personal trainer, membership to an exercise facility, body composition assessment. | Other: High Volume<br>* Participate in one-year high volume (300 minutes per week)aerobic exercise.<br>|
| Active Comparator: Moderate Volume<br>Participate in one year of moderate volume (150 minutes per week) aerobic exercise with free provision of a personal trainer, membership to an exercise facility, body composition assessment. | Other: Moderate Volume<br>* Moderate volume (150 minutes per week) aerobic exercise<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body Fat | Body composition (including weight, hip circumference, waist circumference, waist-hip ratio, total body fat, subcutaneous fat, intra-abdominal fat, lean body mass, body mass index) | 36 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin resistance | Measurements taken of Insulin Levels, Glucose Levels, Insulin Resistance (HOMA Score) | 36 months | 
| Sex Hormone Levels | Measure levels of Estrone, Estradiol, Androstenedione and Testosterone | 36 months | 
| Inflammation | Measure levels of C-Reactive protein, Interleukin-6 and Tumour necrosis factor. | 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prevention and control, Exercise, Sedentary lifestyle, Biological markers