Exercise in Breast Cancer Survivors

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

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

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Behavioral: Aerobic Exercise

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 210
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Norway
  • Oslo, Norway, 0806
    • Norwegian School of Sport Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 28 years to 72 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Aerobic Exercise; 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; 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
No Intervention: Standard care; Participants in this arm will not receive any follow-up on exercise during the intervention period.
Other: Reference Group; 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; 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

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Norwegian School of Sport Sciences
• Collaborators: University of Oslo; Memorial Sloan Kettering Cancer Center; Oslo University Hospital
• Investigators: Principal Investigator: Tormod S Nilsen, PhD, The Norwegian School of Sport Sciences

Study record dates

Study Major Dates

• Study Start (Actual): September 8, 2020
• Primary Completion (Actual): March 2, 2023
• Study Completion (Actual): March 2, 2023

Study Registration Dates

• First Submitted: March 6, 2020
• First Submitted That Met QC Criteria: March 12, 2020
• First Posted (Actual): March 13, 2020

Study Record Updates

• Last Update Posted (Estimate): March 3, 2023
• Last Update Submitted That Met QC Criteria: March 2, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: 2019/1318

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