The Effects of Equivalent Weight Loss With or Without Exercise Training on Breast Cancer Risk (SHAPE-2)

Study Overview
=================
Brief Summary
-----------------
Physical inactivity and overweight are two accepted risk factors for breast cancer. However, because of their correlation it is not clear which is most relevant to risk. The investigators now set out to study whether physical activity in addition to weight loss by diet only, affects sex hormone levels, known to be related to breast cancer risk. In the SHAPE-2 study 250 healthy overweight/obese and physically inactive women are randomly allocated to a diet-induced weight loss group, a combined exercise- and diet-induced weight loss group or a control group. The aim of the first two intervention groups is to loose 5-6 kg of bodyweight, either by dieting or mainly by increased physical activity. Measurements are performed at baseline and after 21 weeks, the end of the study period. The aim of this study is to provide insight into the effect of weight loss mainly driven by exercise compared to equivalent weight loss due to nutritional calorie restriction on breast cancer biomarkers.

Detailed Description
-----------------
Postmenopausal women who are sedentary or overweight, have an increased breast cancer risk. It is suggested that these two factors mediate breast cancer risk mainly through sex hormone-related pathways. However, an inactive lifestyle and obesity are highly correlated and it is not clear which is most relevant to risk. Literature shows that weight loss/ fat loss reduces postmenopausal sex hormone levels, but the question is if there is an additional beneficial effect on hormones of reaching this weight loss by physical activity instead of nutritional interventions. In this three-armed, two-center intervention study, 250 sedentary postmenopausal women who are aged 50-69 years will first enter a run-in period of 5 weeks. During this period, all participants get a diet, adapted to the guidelines for healthy nutrition, meeting their energy expenditures to maintain stable weight. After this run-in phase they are randomly allocated to a (1) diet induced weight loss group, (2) a combined exercise and diet induced weight loss group or (3) a control group. Participants allocated to the dietgroup will get a calorie restricted diet of -500 kCal/day, they will remain their habitual exercise pattern. Participants in the combined group will follow an exercise programme (combined endurance and strength) of 4 hours of sports per week with an average energy expenditure of 350 kCal/day and a, less strict. And a calorie restricted diet of -250 kCal/day. The aim of both intervention groups is to loose 5-6 kg of body weight during the 14 week intervention period. Participants in the control group are requested to retain the baseline diet and their habitual exercise pattern. Primary study parameters measured at baseline and after 21 weeks are: serum concentrations of endogenous estrogens, endogenous androgens and sex hormone binding globulin. Other study parameters include: body fat distribution, amount of total and abdominal fat, weight, BMI, physical fitness, blood pressure and lifestyle factors. The aim of this study is to provide insight into the effect of weight loss mainly driven by exercise compared to equivalent weight loss due to nutritional calorie restriction on breast cancer biomarkers. Furthermore, we are specifically interested whether weight loss mainly due to physical exercise induces greater amounts of fat loss (total and abdominal) and subsequently results in more favourable effects on these hormones compared to equivalent diet-induced weight loss.

Official Title
-----------------
The Effects of Equivalent Weight Loss With or Without Exercise Training on Breast Cancer Risk Biomarkers in Postmenopausal Women: the SHAPE-2 Study

Conditions
-----------------
Breast Cancer Risk

Intervention / Treatment
-----------------
* Behavioral: Diet
* Behavioral: Mainly exercise induced weight loss


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Female 50-69 years of age Postmenopausal (>12 months after last menses) BMI 25-35 kg/m2 Sedentary (<2 hours per week of at least moderately intensive activities (>4 MET)) Willing to be randomly assigned to one of the three study arms Informed consent to participate in all screening and study activities. Exclusion Criteria: Presently using sex-hormones Maintenance use of corticosteroids Suffering cancer (in medical history) except for non-melanoma skin cancers Suffering type II diabetes mellitus or other endocrine related diseases Smoking Alcohol or drug abuse Any disorder that might impede participation in the exercise programme Following, or the intention to follow, a structured weight loss programme elsewhere

Ages Eligible for Study
-----------------
Minimum Age: 50 Years
Maximum Age: 69 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Diet-induced weight loss<br>The diet-induced weight loss group will follow a calorie restricted diet. They are asked to keep their habitual sedentary lifestyle. The aim of this group is to loose 5-6 kg of body weight in 14 weeks time. | Behavioral: Diet<br>* Energy restricted diet, according the national guidelines for healthy nutrition, creating a mean energy deficit of 500 kCal/day.<br>|
| Experimental: Mainly exercise induced weight loss<br>Participants in the exercise- plus diet-induced weight loss group are enrolled in an exercise programme. Next to the exercise programme, they will follow a calorie restricted diet. The aim of this group is to loose 5-6 kg of body weight in 14 weeks time. | Behavioral: Mainly exercise induced weight loss<br>* Exercise programme of 2 hours per week fitness containing endurance and resistance training. And 2 hours of Nordic Walking. Equivalent to an energy expenditure of 350 kCal/day. Next to the exercise programme participants will follow an energy restricted diet according to the national guidelines of healthy nutrition creating an extra energy deficit of 250 kCal/day.<br>|
| No Intervention: Control, stable weight<br>The control group is asked to follow a baseline isocaloric diet and to not change their habitual sedentary lifestyle. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| serum sex hormone levels | Estradiol (total, free), estrone, testosterone, sex hormone binding globulin. | 21 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| anthropometrics and physical fitness. | BMI, weight, waist- and hip-circumference, total body fat (DEXA scan), abdominal fat (subcutaneous and visceral, MRI-abdomen) and physical fitness (maximal exercise capacity test by the ramp protocol). | 21 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Breast cancer, Sex hormones, Physical activity