Resistance and Aerobic Exercise for Prevention in Women With Dense Breasts (REP-D)

The goal of this study is to learn more about how exercise might lower the risk of developing breast cancer in women with dense breast tissue by studying changes that occur in breast tissue and blood as a result of participating in an exercise program.

The names of the study groups in this study are:

• Exercise Training Group
• Waitlist Control Group

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer; Breast Cancer Female
• Intervention / Treatment: Behavioral: Exercise Training Program

Detailed Description

The goal of this study is to learn more about how exercise might lower the risk of developing breast cancer by studying changes that occur in breast tissue and blood as a result of participating in an exercise program. Participants will be placed into one of two study groups: Exercise Training Group vs. Waitlist Control Group. Randomization means that a participant is put into a group by chance.

The research study procedures include screening for eligibility and baseline and end of study assessments which include: breast biopsies, assessment of physical activity habits, aerobic and strength testing, blood draws and questionnaires.

Participants randomized to the exercise group will be expected to participate in exercise sessions throughout the study. They will also be asked to complete logs of their activity.

Participants will be in this research study for up to 16 weeks.

It is expected that 46 women will take part in this study.

The Breast Cancer Research Foundation is supporting this research study by providing funding.

• Study Type: Interventional
• Enrollment (Estimated): 46
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jennifer Ligibel, MD; Phone Number: 617-632-3800; Email: Jennifer_Ligibel@dfci.harvard.edu
• Study Contact Backup: Name: Anna Tanasijevic, MPH; Phone Number: 617-632-5584; Email: anna_tanasijevic@dfci.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Dana Farber Cancer Institute
      • Contact: Jennifer Ligibel, MD; Phone Number: 617-632-3800; Email: Jennifer_Ligibel@dfci.harvard.edu
      • Principal Investigator: Jennifer Ligibel, MD
    • Boston, Massachusetts, United States, 02115
      • Active, not recruiting
      • Brigham and Women's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Women aged 18-59
• Heterogeneously dense/extremely dense (BIRADS 3 or 4) breast tissue on mammogram within the past 12 months
• Physically inactive; engaging in <60 minutes of moderate or vigorous intensity exercise per week, as assessed by Godin Leisure Time screener
• Not pregnant or breastfeeding
• English speaking and able to read English. Investigators are only enrolling English-speaking participants to this study at this time due to the fact that investigators currently only have English-speaking exercise trainers with the proper qualifications to conduct the exercise training
• Written informed consent prior to any study-related procedures

Exclusion Criteria:

• Self-reported inability to walk 2 blocks (at any pace)
• Prior history of breast cancer; prior DCIS is allowable as long as participant is not taking endocrine therapy and has at least 1 breast that has not been irradiated
• On oral or implantable hormonal contraceptives, postmenopausal hormone replacement therapy, a selective estrogen receptor modulator or an aromatase inhibitor; Mirena or other IUD is acceptable
• Consistent strength training in the past 3 months
• Use of weightloss drugs
• Cardiovascular, respiratory or musculoskeletal disease or joint problems that preclude moderate exercise. Examples would include unstable angina, recent myocardial infarction, oxygen-dependent pulmonary disease, and osteoarthritis requiring imminent joint replacement. Moderate arthritis that does not preclude physical activity is not a reason for ineligibility
• Psychiatric disorders or conditions that would preclude participation in the study intervention (e.g. untreated major depression or psychosis, substance abuse, severe personality disorder)

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A: Exercise Intervention; Participants will be randomized and will complete: Baseline study visit with assessments, breast biopsy, and blood draw.; Exercise program for 12 weeks 3x weekly and exercise logs. Additional blood draw after first exercise session.; End of study visit with assessments, breast biopsy, and blood draw.	Behavioral: Exercise Training Program; A 12-week aerobic and resistance-training exercise intervention with a certified exercise trainer in person or virtually. FitBit activity tracker, resistance bands, hand weights, and stationary bike will be provided to participants. Hand weights will be returned at end of study.
No Intervention: Arm B: Waitlist Control; Participants will be randomized and will complete: Baseline study visit with assessments, breast biopsy, and blood draw.; End of study visit with assessments, breast biopsy, and blood draw.; Participants will be offered a complimentary 12-week exercise program after completing the study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Irisin in Exercise Group	Change in circulating irisin at baseline, after 1st exercise session, and end of study in exercise group, and it will be compared using Wilcoxon rank-sum testing. Irisin will be measured by Parallel Reaction Monitoring in the Spiegelman Lab, using the method described by Jedrychowski.	At baseline, within 2 hours of 1st exercise session, and at week 12, up to 16 weeks
Change in Irisin in Control Group	Change in circulating irisin at baseline and end of study in control group, and it will be compared using Wilcoxon rank-sum testing. Irisin will be measured by Parallel Reaction Monitoring in the Spiegelman Lab, using the method described by Jedrychowski.	At baseline and week 12, up to 16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Tissue Markers in Exercise Group	Immunofluorescence analysis of immune and proliferative markers from biopsies of benign breast tissue will be assessed through C-detection by indexing (CODEX) imaging for the exercise group and will be compared between treatments using Wilcoxon rank-sum testing. Imaging to be performed by the Molecular Imaging Core (MIC) at Dana-Farber Cancer Institute.	At baseline and week 12, up to 16 weeks
Change in Tissue Markers in Control Group	Immunofluorescence analysis of immune and proliferative markers from biopsies of benign breast tissue will be assessed through C-detection by indexing (CODEX) imaging for the exercise group and will be compared between treatments using Wilcoxon rank-sum testing. Imaging to be performed by the Molecular Imaging Core (MIC) at Dana-Farber Cancer Institute.	At baseline and week 12, up to 16 weeks
Change in Biomarkers in Exercise Group - Meso scale	Assessed by assays for inflammatory mediators and will be performed using a Meso Scale Discovery multi-plex analysis system and will be conducted by the Translational Research Laboratory at Dana-Farber Cancer Institute.	At baseline and week 12, up to 16 weeks
Change in Biomarkers in Exercise Group - Mass cytometry	Mass cytometry (CyTOF) will be used to evaluate a panel of immune mediators and will be performed in conjunction with the Polyak Laboratory. Wilcoxon rank-sum testing will be used to compare between treatments.	At baseline and week 12, up to 16 weeks
Change in Biomarkers in Control Group - Meso Scale	Assessed by assays for inflammatory mediators and will be performed using a Meso Scale Discovery multi-plex analysis system and will be conducted by the Translational Research Laboratory at Dana-Farber Cancer Institute. Additionally, Mass cytometry (CyTOF) will be used to evaluate a panel of immune mediators and will be performed in conjunction with the Polyak Laboratory. Wilcoxon rank-sum testing will be used to compare between treatments.	At baseline and week 12, up to 16 weeks
Change in Biomarkers in Control Group - Mass cytometry	Mass cytometry (CyTOF) will be used to evaluate a panel of immune mediators and will be performed in conjunction with the Polyak Laboratory. Wilcoxon rank-sum testing will be used to compare between treatments.	At baseline and week 12, up to 16 weeks
Change in Participant Weight in Exercise Group	Defined as the percent change in weight for Exercise Group from pretreatment to week 12 will be calculated, summarized, and compared using Wilcoxon rank-sum testing.	At baseline and week 12, up to 16 weeks
Change in Participant Weight in Control Group	Defined as the percent change in weight for Control Group from pretreatment to week 12 will be calculated, summarized, and compared using Wilcoxon rank-sum testing.	At baseline and week 12, up to 16 weeks
Change in Cardiorespiratory Fitness in Exercise Group	Assessed by VO2 max (i.e., the number of milliliters of oxygen used per kilogram of body weight in one minute (ml/kg/min)), measured using the Sub-Maximal Cycle Ergometer Test, will be calculated and compared using Wilcoxon rank-sum testing.	At baseline and week 12, up to 16 weeks
Change in Cardiorespiratory Fitness in Control Group	Assessed by VO2 max (i.e., the number of milliliters of oxygen used per kilogram of body weight in one minute (ml/kg/min)), measured using the Sub-Maximal Cycle Ergometer Test, will be calculated and compared using Wilcoxon rank-sum testing.	At baseline and week 12, up to 16 weeks
10-Repetition Max Test in Exercise Group	The 10-Repetition Max Test is defined as the heaviest weight a participants could lift for 10 repetitions. Change and relative percent change will be calculated and compared between treatments using Wilcoxon rank-sum testing.	At baseline and week 12, up to 16 weeks
10-Repetition Max Test in Control Group	The 10-Repetition Max Test is defined as the heaviest weight a participants could lift for 10 repetitions. Change and relative percent change will be calculated and compared between treatments using Wilcoxon rank-sum testing.	At baseline and week 12, up to 16 weeks
Change in Minutes of Total Exercise for Exercise Group	Change in minutes of total exercise and met hours per week (7-day par) will be calculated and compared between treatments using Wilcoxon rank-sum testing. The proportion of participants that achieve 150 minutes of exercise per week by 12 weeks will be compared using Wilcoxon rank-sum testing and Fisher's exact tests.	Up to 16 weeks
Change in Minutes of Total Exercise for Control Group	Change in minutes of total exercise and met hours per week (7-day par) will be calculated and compared between treatments using Wilcoxon rank-sum testing. The proportion of participants that achieve 150 minutes of exercise per week by 12 weeks will be compared using Wilcoxon rank-sum testing and Fisher's exact tests.	Up to 16 weeks

Collaborators and Investigators

• Sponsor: Dana-Farber Cancer Institute
• Collaborators: Breast Cancer Research Foundation
• Investigators: Principal Investigator: Jennifer Ligibel, MD, Dana-Farber Cancer Institute

Study record dates

Study Major Dates

• Study Start (Actual): March 28, 2024
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: March 1, 2024
• First Submitted That Met QC Criteria: March 19, 2024
• First Posted (Actual): March 21, 2024

Study Record Updates

• Last Update Posted (Actual): November 21, 2025
• Last Update Submitted That Met QC Criteria: November 19, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Breast Cancer; Breast Cancer Female; Breast Cancer Risk; Dense breast tissue; Dense breasts
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms
• Other Study ID Numbers: 23-676

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: [contact information for Sponsor Investigator or designee]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
• IPD Sharing Time Frame: Data can be shared no earlier than 1 year following the date of publication
• IPD Sharing Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

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