Exercise in Breast Cancer Survivors

Study Overview
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Brief Summary
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The purpose of this study is to compare the effects of aerobic exercise to usual care in women treated with chemotherapy and radiation therapy for non-metastatic breast cancer

Detailed Description
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In this study, we will compare the effects of exercise between women previously treated with breast cancer to women with no history of any cancers. Therefore, in addition to a randomized controlled trial in women with previous breast cancer (i.e., an exerciser group and a control group), we also include a reference group comprising age-matched women with no history of any cancer diagnosis. Women in the reference group will undergo a similar exercise intervention and the exercise group. This study recruits through invitation only. The primary endpoint in this study is the change in cardiorespiratory fitness, measured as VO2peak. Secondary endpoints include common risk factors for cardiovascular disease and cardiometabolic health, endpoints derived from the cardiopulmonary exercise test and lung function assessments, cellular muscle endpoints derived from muscle biopsies obtained from m. vastus lateralis, also patient-reported outcomes.

Official Title
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The Cause Trial: A Randomized Trial of Aerobic Exercise on CVD Risk Factors in Breast Cancer Survivors

Conditions
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Breast Cancer

Intervention / Treatment
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* Behavioral: Aerobic Exercise


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eligible BCS must be listed in the Norwegian Cancer registry Female Adult-onset breast cancer diagnosis, diagnosed between 2008 and 2012 60 years or younger at the time of diagnosis received anthracycline-based chemotherapy as a part of their treatment history signed informed consent and medical doctors approveal of participation prior to inclusion Exclusion Criteria: Received Herceptin Diagnosed with stage IV breast cancer Relapse since diagnosis A history, or current presence, of another diagnosis of invasive cancer of any kind Selfreported severe fatigue present with any uncontrolled- or recent cardiovascular disease, has undergone heart surgery or uses a pacemaker currently exercising more than 90 minutes per week

Ages Eligible for Study
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Minimum Age: 28 Years
Maximum Age: 72 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aerobic Exercise<br>The aim is for participants to complete three weekly sessions of supervised aerobic treadmill based exercise for five months. Session duration varies from 20-60 minutes, with exercise intensity ranging from 55-95% of peak heart rate. Maximal exercise capacity (VO2peak and peak heart rate), will be determined by the CPET performed by certified exercise physiologists at baseline. | Behavioral: Aerobic Exercise<br>* Participants will be randomized to supervised aerobic exercise or standard care. Women with no current or past malignant disease will comprise the reference group and will be matched for age to participants in the Aerobic Exercise arm<br>|
| No Intervention: Standard care<br>Participants in this arm will not receive any follow-up on exercise during the intervention period. | |
| Other: Reference Group<br>Participants in this arm are age-matched women with no history of any malignant disease, which will undergo similar assessments at baseline and post-intervention and also follow similar exercise intervention as the breast cancer survivors randomized to the Aerobic exercise arm | Behavioral: Aerobic Exercise<br>* Participants will be randomized to supervised aerobic exercise or standard care. Women with no current or past malignant disease will comprise the reference group and will be matched for age to participants in the Aerobic Exercise arm<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in VO2peak | Peak oxygen uptake during a treadmill based cardiopulmonary exercise test | From baseline to five months (post-intervention) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Systolic- and diastolic heart chamber dimensions | Cardiac morphology and function will be assessed by 2D and 3D Echocardiography and 2D strain echocardiography | From baseline to five months (post-intervention) | 
| Systolic- and diastolic longitudinal strain | Cardiac morphology and function will be assessed by 2D and 3D Echocardiography and 2D strain echocardiography | From baseline to five months (post-intervention) | 
| Lean body mass | Body composition will be assessed by dual x-ray absorptiometry | From baseline to five months (post-intervention) | 
| Fat mass | Body composition will be assessed by dual x-ray absorptiometry | From baseline to five months (post-intervention) | 
| Blood volume | Hemoglobin mass and blood volume will be assessed using the carbon monoxide rebreathing method | From baseline to five months (post-intervention) | 
| Muscle fiber type | Change in muscle morphology will be assessed in muscle biopsies using immunohistochemistry | From baseline to five months (post-intervention) | 
| Muscle fiber area | Change in muscle morphology will be assessed in muscle biopsies using immunohistochemistry | From baseline to five months (post-intervention) | 
| Muscle mitochondria mass | Change in mitochondrial proteins will be assessed in muscle biopsies using western blot | From baseline to five months (post-intervention) | 
| Quality of life: Quality of Life Questionnaire (QLQ) C-30 | Relevant patient reported outcomes will be obtained using validated Quality of Life Questionnaire (QLQ) C-30 | From baseline to five months (post-intervention) | 
| Genome-wide DNA methylation and gene expression | For a sub-group of participants, muscle biopsies will be further processed for RNA and DNA | From baseline to five months (post-intervention) |