Understanding and Predicting Breast Cancer Events After Treatment

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Understanding and Predicting Breast Cancer Events After Treatment (UPBEAT)

Conditions
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Breast Cancer

Intervention / Treatment
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* Diagnostic Test: Cardiac MRI


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Breast Cancer Patients<br>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<br>* 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.<br>|
| Experimental: Non-Cancer Controls<br>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<br>* 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.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast Cancer, Fatigue, Cardiovascular Events