Breast Cancer, Cardiotoxicity, Disability Physical, Heart Failure
Conditions
Keywords
Exercise Training, Fitness, Heart, Muscle, Cancer, Survivorship
Brief summary
The chemotherapy medications used for breast cancer treatment are important for achieving a cure, but a potential side effect is that they can cause a decline in functional capacity (reduced exercise tolerance and impaired physical function) and increase the risk of cardiovascular disease. The risks of decreased functional capacity and cardiovascular disease are highest in breast cancer survivors as they grow older. The factors causing the decline in functional capacity are not well understood, however they may be related to a reduction in cardiac function (e.g. decreased pumping ability of the heart) or skeletal muscle function (reduced muscle blood flow and oxygenation). Exercise training is used for other populations at risk for cardiovascular disease (such as cardiac rehabilitation), but is not routinely offered to breast cancer survivors. Therefore this research study wants to test whether exercise training can improve heart and muscle health, and increase functional capacity in up to 60 older breast cancer survivors aged \>60 years old who previously received chemotherapy drugs that can affect the heart. The purpose of this study is to compare two rehabilitation approaches: a 12-week structured exercise training program or a 12-week stretching-yoga program. The investigators want to compare whether these programs can improve functional capacity, and heart and skeletal muscle function. To do this, some of the participants in this study will be randomly enrolled in the structured exercise training program and others will be randomly enrolled in the stretching-yoga program.
Interventions
BEHAVIORALStructured Exercise Training
Participants will complete 12-weeks of supervised, structured moderate-to-high intensity aerobic and resistance training three times per week.
BEHAVIORALGroup-based Yoga and Stretching
Participants will complete 12-weeks of supervised group-based yoga and stretching once per week.
Sponsors
Canadian Institutes of Health Research (CIHR)
University of Alberta
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
SINGLE (Outcomes Assessor)
Masking description
All MRI outcomes will be performed blinded to group allocation. Outcome assessors for post-outcome assessments will be blinded to baseline values.
Eligibility
Sex/Gender
FEMALE
Age
60 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥60 years * Previously diagnosed with early-stage (I-III) BC * Completed (≥1 year post) primary cardiotoxic treatment (anthracycline-based chemotherapy or trastuzumab-based biological therapy).
Exclusion criteria
* Have a history of coronary artery disease, heart failure, persistent and permanent arrhythmia (e.g. currently in atrial fibrillation), stroke, or chronic obstructive pulmonary disease * Develop signs or symptoms of myocardial ischemia (≥1mm horizontal or down-sloping ST segment depression on electrocardiogram) during the cardiopulmonary (VO2peak) test * Have any research MRI contraindications (e.g. any type of pacemaker), or any orthopedic limitation preventing exercise testing * Currently performing structured exercise training (defined as ≥30 mins/day of moderate-to-vigorous aerobic and/or resistance exercise training on ≥4 days/week) * Are unwilling to be randomized to either ExT or STRETCH
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Peak arterio-venous oxygen content difference | 12 Weeks | Peak exercise arterio-venous oxygen content difference assessed using whole-body exercise MRI |
| Peak cardiac output | 12 Weeks | Peak exercise cardiac output assessed using whole-body exercise MRI |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Peak stroke volume | 12 Weeks | Peak exercise stroke volume assessed using whole-body exercise MRI |
| Aerobic endurance | 12 Weeks | Walk distance measured during a six minute walk test |
| Physical Function | 12 Weeks | Short physical performance battery total score (Score from 0 to 12, where higher scores represent better function) |
| Skeletal muscle volume | 12 Weeks | Muscle volume of the thigh and lower leg from MRI |
| Skeletal muscle myosteatosis | 12 Weeks | Muscular fat fraction of the thigh and lower leg from MRI |
| Skeletal muscle fibrosis | 12 Weeks | Muscular fibrosis of the thigh and lower leg measured from MRI T1 values |
| Calf muscle aerobic capacity | 12 Weeks | Peak muscle oxygen uptake from maximal plantar flexion exercise MRI |
| Calf muscle oxygen extraction | 12 Weeks | Peak muscle arterio-venous oxygen difference from maximal plantar flexion exercise MRI |
| Calf muscle oxygen diffusive conductance | 12 Weeks | Peak muscle oxygen diffusive conductance from maximal plantar flexion exercise MRI |
| Calf muscle metabolism | 12 Weeks | Exercise phosphate and phosphocreatine responses during plantar flexion exercise 31P magnetic resonance spectroscopy |
| 10-year Framingham Risk Score | 12 Weeks | 10-year Framingham Risk Score will be calculated from participant Sex, Age, HDL-cholesterol, Total Cholesterol, Resting Systolic Blood Pressure, Smoking Status and presence of Diabetes. The score ranges from 0% to 100% where higher scores indicate higher CVD risk. |
| Peak volume of oxygen uptake | 12 Weeks | Peak volume of oxygen uptake assessed from a maximal cardiopulmonary exercise test |
| Peak diffusive muscle oxygen conductance | 12 Weeks | Calculated diffusive muscle oxygen conductance assessed using whole-body exercise MRI |
Other
| Measure | Time frame | Description |
|---|---|---|
| Habitual Physical Activity | 12 Weeks | Time spent in moderate-to-vigorous physical activity over 7 days of objective monitoring (Fitbit) |
| Fasting Lipids | 12 Weeks | A fasting blood test will be used to measure concentrations of high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, total cholesterol and triglycerides |
| Fasting Glycaemic Control | 12 Weeks | A fasting blood test will be used to measure concentrations of fasting plasma glucose and fasting insulin |
| Fasting Insulin Resistance | 12 Weeks | Fasting insulin resistance will be calculated from fasting plasma glucose and insulin concentrations using the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) method. |
| C-reactive protein | 12 Weeks | Plasma concentrations of C-reactive protein will be assessed from a fasting blood test. |
| Resting blood pressure | 12 Weeks | Resting systolic and diastolic blood pressure will be measured in the supine position using an automated oscillometric blood pressure cuff. |
| Functional Assessment of Cancer Therapy - Breast (FACT-B) Questionnaire | 12 Weeks | Quality of Life, including physical, emotional and social wellbeing and breast cancer related symptom score on the FACT-B questionnaire. Participants will be scored from 0 to 148, where 148 represents the highest quality of life. |
Countries
Canada
Contacts
Primary ContactNathan Weeldreyer, PhD
Outcome results
None listed