Understanding and Predicting Breast Cancer Events After Treatment (UPBEAT)

Understanding and Predicting Breast Cancer Events After Treatment (UPBEAT)

This study is being done to see if patients receiving chemotherapy for breast cancer affects the heart, the ability to exercise and fatigue when compared to patients who do not have cancer.

Study Overview

• Status: Active, not recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Diagnostic test: Cardiac MRI

Detailed Description

840 women aged ≥18 years old scheduled to receive chemotherapy for Stage I-III breast cancer and a comparison population of 160 women without cancer (1,000 total). Equal numbers of women will be recruited aged < 52 vs. > 52. At baseline, innovative MRI measures of CV function (LV and aorta); measurements of submaximal (6-minute walk) and, on 45% of the cohort, maximal (peak VO2) exercise capacity; questionnaire data to assess fatigue and behavioral and psychosocial risk factors; and biomarkers will be collected.

Measurements will be repeated at 3±1, 12±2 and 24±2 months. This study will assess the relevance of pre-existing factors such as age, black/white race, hypertension, smoking (yes/no), diabetes, coronary artery disease, menopause status, CV medications, and physical activity on the study outcomes. Also, this study will assess dynamic change in modifiable CV risk factors (including BMI, blood pressure, serum lipids, serum glucose, physical activity, psychosocial factors, lifestyle behaviors), and the cancer treatment including chemotherapy, radiation therapy, immunotherapy, and surgery.

• Study Type: Interventional
• Enrollment (Actual): 403
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham Cancer Center
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • MedStar Washington Hospital Center
  • Florida
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center - McKinley Campus
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
  • Indiana
    • Carmel, Indiana, United States, 46032
      • IU Health North Hospital
    • Indianapolis, Indiana, United States, 46202
      • Indiana University/Melvin and Bren Simon Cancer Center
    • Indianapolis, Indiana, United States, 46290
      • Springmill Medical Center
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Cancer Center
    • Westwood, Kansas, United States, 66205
      • University of Kansas Hospital-Westwood Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Comprehensive Cancer Center
    • Dearborn, Michigan, United States, 48124
      • Beaumont Hospital - Dearborn
    • Farmington Hills, Michigan, United States, 48336
      • Beaumont Hospital - Farmington Hills
    • Grand Rapids, Michigan, United States, 49503
      • Spectrum Health at Butterworth Campus
    • Royal Oak, Michigan, United States, 48073
      • William Beaumont Hospital-Royal Oak
    • Troy, Michigan, United States, 48085
      • William Beaumont Hospital - Troy
  • Minnesota
    • Maplewood, Minnesota, United States, 55109
      • Saint John's Hospital - Healtheast
    • Minneapolis, Minnesota, United States, 55407
      • Abbott-Northwestern Hospital
    • Minneapolis, Minnesota, United States, 55454
      • Health Partners Inc
    • Saint Paul, Minnesota, United States, 55101
      • Regions Hospital
    • Saint Paul, Minnesota, United States, 55102
      • United Hospital
    • Woodbury, Minnesota, United States, 55125
      • Minnesota Oncology Hematology PA-Woodbury
  • New Jersey
    • Morristown, New Jersey, United States, 07960
      • Morristown Medical Center
    • Newton, New Jersey, United States, 07860
      • Newton Medical Center
    • Summit, New Jersey, United States, 07902
      • Overlook Hospital
  • North Carolina
    • Asheboro, North Carolina, United States, 27203
      • Randolph Hospital
    • Burlington, North Carolina, United States, 27215
      • Cone Health Cancer Center at Alamance Regional
    • Charlotte, North Carolina, United States, 28204
      • Novant Health Presbyterian Medical Center
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Greensboro, North Carolina, United States, 27403
      • Cone Health Cancer Center
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences
  • Pennsylvania
    • Harrisburg, Pennsylvania, United States, 17109
      • UPMC Pinnacle Cancer Center/Community Osteopathic Campus
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania/Abramson Cancer Center
    • York, Pennsylvania, United States, 17408
      • UPMC Memorial
  • South Carolina
    • Boiling Springs, South Carolina, United States, 29316
      • Prisma Health Cancer Institute - Spartanburg
    • Easley, South Carolina, United States, 29640
      • Prisma Health Cancer Institute - Easley
    • Greenville, South Carolina, United States, 29605
      • Prisma Health Cancer Institute - Faris
    • Greenville, South Carolina, United States, 29615
      • Prisma Health Cancer Institute - Eastside
    • Greenville, South Carolina, United States, 29605
      • Prisma Health Cancer Institute - Butternut
    • Greenville, South Carolina, United States, 29605
      • Prisma Health Greenville Memorial Hospital
    • Greer, South Carolina, United States, 29650
      • Prisma Health Cancer Institute - Greer
    • Seneca, South Carolina, United States, 29672
      • Prisma Health Cancer Institute - Seneca
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern/Simmons Cancer Center-Dallas
  • Virginia
    • Lynchburg, Virginia, United States, 24501
      • Centra Lynchburg Hematology-Oncology Clinic Inc
    • Richmond, Virginia, United States, 23235
      • VCU Massey Cancer Center at Stony Point
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University/Massey Cancer Center
    • Richmond, Virginia, United States, 23230
      • Virginia Cancer Institute
    • Winchester, Virginia, United States, 22601
      • Shenandoah Oncology PC
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center - Montlake
  • Wisconsin
    • Burlington, Wisconsin, United States, 53105
      • Aurora Cancer Care-Southern Lakes VLCC
    • Fond Du Lac, Wisconsin, United States, 54937
      • Aurora Health Center-Fond du Lac
    • Germantown, Wisconsin, United States, 53022
      • Aurora Health Care Germantown Health Center
    • Grafton, Wisconsin, United States, 53024
      • Aurora Cancer Care-Grafton
    • Green Bay, Wisconsin, United States, 54311
      • Aurora BayCare Medical Center
    • Kenosha, Wisconsin, United States, 53142
      • Aurora Cancer Care-Kenosha South
    • Milwaukee, Wisconsin, United States, 53209
      • Aurora Cancer Care-Milwaukee
    • Milwaukee, Wisconsin, United States, 53215
      • Aurora Saint Luke's Medical Center
    • Milwaukee, Wisconsin, United States, 53233
      • Aurora Sinai Medical Center
    • Oshkosh, Wisconsin, United States, 54904
      • Vince Lombardi Cancer Clinic - Oshkosh
    • Racine, Wisconsin, United States, 53406
      • Aurora Cancer Care-Racine
    • Sheboygan, Wisconsin, United States, 53081
      • Vince Lombardi Cancer Clinic-Sheboygan
    • Summit, Wisconsin, United States, 53066
      • Aurora Medical Center in Summit
    • Two Rivers, Wisconsin, United States, 54241
      • Vince Lombardi Cancer Clinic-Two Rivers
    • Wauwatosa, Wisconsin, United States, 53226
      • Aurora Cancer Care-Milwaukee West
    • West Allis, Wisconsin, United States, 53227
      • Aurora West Allis Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria for Women with Stage I - III Breast Cancer:

• Stage I-III female breast cancer (including inflammatory and newly diagnosed or locally recurrent breast cancer) but not metastatic breast cancer being treated with curative intent
• > 18 years old
• Scheduled to receive chemotherapy and/or estrogen antagonist aromatase inhibitors (anastrozole [Arimidex], letrozole [Femara], exemestane [Aromasin]).
• Able to hold breath for 10 seconds
• ECOG performance status 0 -2
• Able to walk at least 2 blocks without chest pain, dyspnea, shortness of breath or fainting
• Able to exercise on a treadmill or stationary cycle
• Participants in other ongoing clinical trials are eligible for this study

Exclusion Criteria for Women with Stage I-III Breast Cancer:

• Those with ferromagnetic cerebral aneurysm clips or other intracranial metal; pacemakers, defibrillators, functioning neurostimulator devices or other implanted non-compatible MRI devices (patients with tissue expanders will not be excluded)
• If previously measured, known LVEF <50%
• Symptomatic claustrophobia
• Unable to provide informed consent
• At the beginning of the study, pregnant women and women who are breast-feeding will not be enrolled.
• Severe pulmonary hypertension

• Within the past 6 months:

  • Acute pulmonary embolus
  • Deep vein thrombosis

• Within the past month:

  • Heart attack
  • Unstable or stable angina (cardiac chest pain)
  • Left main coronary artery disease
  • Symptomatic heart failure
  • Uncontrolled hypertension (SBP > 180 mm Hg or DBP > 120 mm Hg)
  • Severe valvular heart disease
  • Uncontrolled metabolic disease (diabetes with fasting BS >300 mg/dl, thyrotoxicosis, myxedema)
  • Aortic aneurism (>45 mm diameter) or aortic dissection
  • Uncontrolled slow or fast heart rhythm causing symptoms or hemodynamic compromise
  • Hypertrophic obstructive cardiomyopathy
• Patient does not understand English

Inclusion Criteria for Women Free of Cancer for Comparison:

• Healthy female without known coronary artery disease > 18 years old
• Able to hold breath 10 seconds
• ECOG performance status = 0 or 1
• Able to walk at least 2 blocks without chest pain, dyspnea, shortness of breath or fainting
• Able to exercise on a treadmill or stationary cycle
• No personal history of cancer other than superficial skin cancers
• Has never received chemotherapy, radiation therapy, immunotherapy, or had breast cancer related surgery
• If previously measured, LVEF ≥ 50%

Exclusion Criteria for Women Free of Cancer for Comparison:

• Inflammatory conditions such as lupus or inflammatory bowel disease
• Overt coronary artery disease or heart failure
• Those with ferromagnetic cerebral aneurysm clips or other intracranial metal; pacemakers, defibrillators, functioning neurostimulator devices or other implanted non-compatible MRI devices
• Symptomatic claustrophobia
• Unable to provide informed consent
• At the beginning of the study, pregnant women or women who are breast feeding will not be enrolled.
• Severe pulmonary hypertension

• Within the past 6 months:

  • Acute pulmonary embolus
  • Deep vein thrombosis

• Within the past month:

  • Heart attack
  • Unstable or stable angina (cardiac chest pain)
  • Left main coronary artery disease
  • Symptomatic heart failure
  • Uncontrolled hypertension (SBP > 180 mm Hg or DBP > 120 mm Hg)
  • Severe valvular heart disease
  • Uncontrolled metabolic disease (diabetes with fasting BS >300 mg/dl, thyrotoxicosis, myxedema)
  • Aortic aneurism (>45 mm diameter) or aortic dissection
  • Uncontrolled slow or fast heart rhythm causing symptoms or hemodynamic compromise
  • Hypertrophic obstructive cardiomyopathy
• Patient does not understand English

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Breast Cancer Patients; Breast cancer patients receiving non-anthracycline or anthracycline chemotherapy Cardiac MRIs will be performed baseline, 3 months (for cancer patients only), and 24 months. Baseline: Collect innovative MRI measures of CV function (LV and aorta); measurements of submaximal (6-minute walk) and, on 45% of the cohort, maximal (peak VO2) exercise capacity; questionnaire data to assess fatigue and behavioral and psychosocial risk factors; and biomarkers. Measurements will be repeated at 3±1, 12±2 and 24±2 months after initiation of chemotherapy treatment.	Diagnostic test: Cardiac MRI; Breast Cancer Patients Cardiac MRIs will be performed baseline, 3 months (for cancer patients only), and 24 months. Non-Cancer Controls Cardiac MRIs will be performed baseline and 24 months.
Experimental: Non-Cancer Controls; Non-Cancer Controls Cardiac MRIs will be performed baseline and 24 months. Baseline: Collect innovative MRI measures of CV function (LV and aorta); measurements of submaximal (6-minute walk) and, 45% of the cohort, maximal (peak VO2) exercise capacity; questionnaire data to assess fatigue and behavioral and psychosocial risk factors; and biomarkers. Measurements will be repeated at 3±1, 12±2 (after the completion of radiation) and 24±2 months after initiation of baseline activities.	Diagnostic test: Cardiac MRI; Breast Cancer Patients Cardiac MRIs will be performed baseline, 3 months (for cancer patients only), and 24 months. Non-Cancer Controls Cardiac MRIs will be performed baseline and 24 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
FACT-Fatigue	Participants rate the degree to which each item applies in the past 7 days prior to Baseline using a 5-point scale. Scores range from 0-52, with higher scores indicating greater fatigue.	Baseline
Change in FACT-Fatigue Results	Participants rate the degree to which each item applies in the past 7 days using a 5-point scale. Scores range from 0-52, with higher scores indicating greater fatigue.	Baseline and 3 months
Change in FACT-Fatigue Results	Participants rate the degree to which each item applies in the past 7 days using a 5-point scale. Scores range from 0-52, with higher scores indicating greater fatigue.	Baseline, 3 months and 12 months
Change in FACT-Fatigue Results	Participants rate the degree to which each item applies in the past 7 days using a 5-point scale. Scores range from 0-52, with higher scores indicating greater fatigue.	Baseline, 3 months, 12 months and 24 months
Change in MRI Exam Results	The exam will measure left ventricular volumes, ejection fraction, myocardial strain/strain rate, mass, mapping, aortic pulse wave velocity and aortic wall thickness. The exam will take 10 - 15 minutes to complete.	Baseline, 3 months and 24 months
Change in 6 Minute Walk Results	The purpose of this test is to find out how far the participant can walk in 6 minutes.	Baseline, 3 months, 12 months and 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cohen's 4-item Perceived Stress Scale (PSS)	A summed scale asking how often over the prior two weeks four aspects of stress were experienced (1=never to 5=very often) o weeks four aspects of stress were experienced (1=never to 5=very often)	Baseline, 3 months, 12 months, and 24 months
Cook-Medley Hostility Scale	A 14-item scale used to assess the effect of hostility associated with cardiovascular risk factors. Minimum Score: 0 Maximum Score: 13 Higher values indicate greater hostility.	Baseline
Changes in FACT-Fatigue Results	Participants rate the degree to which each item applies in the past 7 days using a 5-point scale. Scores range from 0-52, with higher scores indicating greater fatigue.	Baseline, 3 months, 12 months, and 24 months
6 Minute Walk Results	The purpose of this test is to find out how far the participant can walk in 6 minutes.	Baseline, 3 months, 12 months and 24 months
RAND MOS 36-item Short Form Health Survey (SF-36)	SF-36 consists of 36 items measuring the following 8 domains: physical function, role limitations due to physical health problems, bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional health problems, and mental health. These 8 domains also provide two summary scores.	Baseline, 3 months, 12 months and 24 months
Center for Epidemiological Studies Depression Scale (CESD-10)	Screening questionnaire assessing depressive symptoms during the last week	Baseline, 3 months, 12 months and 24 months
Godin Leisure-Time Exercise Questionnaire (LTEQ)	Main process measure of physical activity participation	Baseline, 3 months, 12 months and 24 months
PACE Adult Sedentary Behaviors Survey	Assess sedentary lifestyle behaviors	Baseline, 3 months, 12 months and 24 months
PROMIS Short Form 8A Measure of Sleep Disturbance	Assess time course and risk factors associated with sleep disturbance and fatigue Minimum Score: Raw: 8, T-score: 28.9 Maximum Score: Raw: 40, T-score: 76.5 Higher values represent greater sleep disturbance.	Baseline, 3 months, 12 months and 24 months
PROMIS Applied Cognitive Abilities Short Form 8A and Applied Cognition General Concerns Short Form 8A	Measurement of different aspects of cognitive functioning. PROMIS Applied Cognitive Abilities Short Form 8A - Minimum Score: Raw: 8, T-score: 27.0 Maximum Score: Raw: 40, T-score: 64.8 Higher values represent better cognition. Applied Cognition General Concerns Short Form 8A - Minimum Score: Raw: 8, T-score: 23.3 Maximum Score: Raw: 40, T-score: 62.7 Higher values represent better cognition.	Baseline, 3 months, 12 months and 24 months
Walking Efficacy for Duration Scale	Comprised of six items and will be included as a measure of exercise capacity	Baseline, 3 months, 12 months and 24 months
Chair Stands - Measures Leg Strength	Participants will be first asked to stand from a sitting position without using their arms. If they can perform the task, they will then be asked to stand up and sit down five times as quickly as possible. The time to complete the task will be recorded.	Baseline, 3 months, 12 months and 24 months
Standing Balance Test	Participants will be asked to maintain balance for up to 30 seconds in three positions characterized by a progressive narrowing of the base support.	Baseline, 3 months, 12 months and 24 months
Gait Speed Test	Participants will be instructed to start at a marked walking course with toes touching the start line and when cued to start, will begin walking at their ususal speed. The time to walk from the starting line to the end of the 4-meter walk will be recorded.	Baseline, 3 months, 12 months and 24 months
Grip Strength	Grip strength is assessed with an isometric handgrip dynamometer while the participant is sitting with the head facing straight ahead. The elbow should be bent at a 90 degree angle and the wrist should be at the mid-prone position.	Baseline, 3 months, 12 months and 24 months
Range of Motion	Range of motion at the shoulder joint will be assessed with shoulder flexion and shoulder abduction with a goniometer.	Baseline, 3 months, 12 months and 24 months
KCCQ-12 Questionnaire	Independently measures the patient's perception of their health status which includes heart failure symptoms (frequency and burden), physical and social limitations, and how their heart failure impacts their QOL within a 2-week recall period.	Baseline, 24 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
B-type natriuretic peptide (BNP)	Serum BNP as a predictor of exercise intolerance	Baseline and 24 months
Troponin - 1	Acquired to determine associations between troponin levels during therapy and the onset of cardiac and vascular dysfunction, exercise capacity, and fatigue.	Baseline and 3 months

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Gregory Hundley, MD, Wake Forest University Health Sciences

Publications and helpful links

General Publications

• Bellissimo MP, Canada JM, Jordan JH, Ladd AC, Heiston EM, Brubaker P, Mihalko SL, Reding K, D Agostino R, O Connell N, Hackney MH, Weaver KE, Lesser GJ, Avis NE, Hundley WG. Changes in Physical Activity, Functional Capacity, and Cardiac Function during Breast Cancer Therapy. Cancer Epidemiol Biomarkers Prev. 2022 Jul 1;31(7):1509. doi: 10.1158/1055-9965.EPI-22-0470.

Study record dates

Study Major Dates

• Study Start (Actual): July 21, 2017
• Primary Completion (Estimated): November 30, 2024
• Study Completion (Estimated): July 31, 2034

Study Registration Dates

• First Submitted: May 20, 2016
• First Submitted That Met QC Criteria: May 31, 2016
• First Posted (Estimated): June 7, 2016

Study Record Updates

• Last Update Posted (Actual): January 24, 2024
• Last Update Submitted That Met QC Criteria: January 23, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Breast Cancer; Fatigue; Cardiovascular Events
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: IRB00045463; WF 97415 (Other Identifier: Sponsor); 1R01CA199167-01 (U.S. NIH Grant/Contract); NCI-2017-00386 (Registry Identifier: NCI CTRP)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Wake Forest NCORP Research Base is committed to following the NIH Statement on Sharing Research Data (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-032.html). As of July 2018, the WF NCORP RB signed an agreement with NCI to contribute de-identified data and data dictionaries from clinical trials conducted through our RB to the NCI NCTN/NCORP data archive within 6 months of primary and non-primary publications of phase II/III and phase III trials to https://nctn-data-archive.nci.nih.gov/. This will become the primary means for sharing raw data, and we will adhere to the guidelines spelled out in the NCTN/NCORP Data Archive Usage Guide. De-identified data from studies not covered by the agreement (e.g., phase II and observational studies) will be made available upon request. All data files will be de-identified. De-identification procedures will meet the HIPAA criteria as detailed in the Code of Federal Regulations, Part 45, Section 164.514.
• IPD Sharing Time Frame: 6 months after publication for a 2 year duration
• IPD Sharing Access Criteria: upon request to NCORP@wakehealth.edu

Drug and device information, study documents

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