Breast cancEr, FITness and ExeRcise for Heart Health: The BE-FITTER Study (BE-FITTER)

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.

Study Overview

• Status: Recruiting
• Conditions: Heart Failure; Breast Cancer; Cardiotoxicity; Disability Physical
• Intervention / Treatment: Behavioral: Structured Exercise Training; Behavioral: Group-based Yoga and Stretching

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Nathan Weeldreyer, PhD; Phone Number: 616.566.6756; Email: ageheart@ualberta.ca

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G1C9
      • Recruiting
      • University of Alberta
      • Principal Investigator: Mark Haykowsky, PhD
      • Sub-Investigator: Edith Pituskin, PhD
      • Sub-Investigator: Richard B Thompson, PhD
      • Sub-Investigator: Margaret McNeely, PhD
      • Contact: Nathan Weeldreyer, PhD; Phone Number: 616.566.6756; Email: ageheart@ualberta.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental Arm: Structured Exercise Training; Participants randomized to exercise training will be provided with a 12-week structured exercise training program. The program includes 3 weekly sessions of aerobic exercise (e.g treadmill, cycling, elliptical machine) and/or resistance training (i.e lifting weights). The aerobic sessions will include long-endurance (40-60 minutes at moderate intensity), tempo (30-40 minutes at a moderate-vigorous intensity) and high-intensity interval exercise (10-15 intervals of 30-60 seconds at 100% peak aerobic power output, interspersed with 60 seconds of active recovery). Resistance training will include 4-6 lower body exercises performed for 2-3 sets of 8-20 repetitions at a load equivalent to 60-85% of their one repetition maximum. The program will be supervised by an exercise trainer (Clinical Exercise Physiologist, Physiotherapist, Kinesiologist or Research Associate with exercise training experience) and will be individualized each individual's baseline fitness and medical history.	Behavioral: Structured Exercise Training; Participants will complete 12-weeks of supervised, structured moderate-to-high intensity aerobic and resistance training three times per week.
Active Comparator: Active Comparator: Group-based Yoga and Stretching; Participants allocated to the yoga and stretching group will provided with a once weekly yoga and stretching group class. The classes will consist of a combination of light-intensity yoga, balance and stretching exercises. The yoga and stretching class will be overseen by a yoga instructor, physiotherapist, physiotherapy trainee or research assistant with exercise training background	Behavioral: Group-based Yoga and Stretching; Participants will complete 12-weeks of supervised group-based yoga and stretching once per week.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak arterio-venous oxygen content difference	Peak exercise arterio-venous oxygen content difference assessed using whole-body exercise MRI	12 Weeks
Peak cardiac output	Peak exercise cardiac output assessed using whole-body exercise MRI	12 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak volume of oxygen uptake	Peak volume of oxygen uptake assessed from a maximal cardiopulmonary exercise test	12 Weeks
Peak diffusive muscle oxygen conductance	Calculated diffusive muscle oxygen conductance assessed using whole-body exercise MRI	12 Weeks
Peak stroke volume	Peak exercise stroke volume assessed using whole-body exercise MRI	12 Weeks
Aerobic endurance	Walk distance measured during a six minute walk test	12 Weeks
Physical Function	Short physical performance battery total score (Score from 0 to 12, where higher scores represent better function)	12 Weeks
Skeletal muscle volume	Muscle volume of the thigh and lower leg from MRI	12 Weeks
Skeletal muscle myosteatosis	Muscular fat fraction of the thigh and lower leg from MRI	12 Weeks
Skeletal muscle fibrosis	Muscular fibrosis of the thigh and lower leg measured from MRI T1 values	12 Weeks
Calf muscle aerobic capacity	Peak muscle oxygen uptake from maximal plantar flexion exercise MRI	12 Weeks
Calf muscle oxygen extraction	Peak muscle arterio-venous oxygen difference from maximal plantar flexion exercise MRI	12 Weeks
Calf muscle oxygen diffusive conductance	Peak muscle oxygen diffusive conductance from maximal plantar flexion exercise MRI	12 Weeks
Calf muscle metabolism	Exercise phosphate and phosphocreatine responses during plantar flexion exercise 31P magnetic resonance spectroscopy	12 Weeks
10-year Framingham Risk Score	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.	12 Weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Habitual Physical Activity	Time spent in moderate-to-vigorous physical activity over 7 days of objective monitoring (Fitbit)	12 Weeks
Fasting Lipids	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	12 Weeks
Fasting Glycaemic Control	A fasting blood test will be used to measure concentrations of fasting plasma glucose and fasting insulin	12 Weeks
Fasting Insulin Resistance	Fasting insulin resistance will be calculated from fasting plasma glucose and insulin concentrations using the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) method.	12 Weeks
C-reactive protein	Plasma concentrations of C-reactive protein will be assessed from a fasting blood test.	12 Weeks
Resting blood pressure	Resting systolic and diastolic blood pressure will be measured in the supine position using an automated oscillometric blood pressure cuff.	12 Weeks
Functional Assessment of Cancer Therapy - Breast (FACT-B) Questionnaire	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.	12 Weeks

Collaborators and Investigators

• Sponsor: University of Alberta
• Collaborators: Canadian Institutes of Health Research (CIHR)

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2024
• Primary Completion (Estimated): December 20, 2026
• Study Completion (Estimated): December 20, 2026

Study Registration Dates

• First Submitted: May 6, 2024
• First Submitted That Met QC Criteria: September 10, 2024
• First Posted (Actual): September 19, 2024

Study Record Updates

• Last Update Posted (Actual): January 8, 2026
• Last Update Submitted That Met QC Criteria: January 5, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Cancer; Exercise Training; Fitness; Heart; Survivorship; Muscle
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Wounds and Injuries; Pathologic Processes; Neoplasms by Site; Heart Diseases; Chemically-Induced Disorders; Skin Diseases; Breast Diseases; Drug-Related Side Effects and Adverse Reactions; Radiation Injuries; Pathological Conditions, Signs and Symptoms; Skin and Connective Tissue Diseases; Neoplasms; Heart Failure; Breast Neoplasms; Cardiotoxicity
• Other Study ID Numbers: HREBA.CC-24-0058

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No