Women In Steady Exercise Research - Window of Opportunity for Exercise and Tumor Biology

Study Overview
=================
Brief Summary
-----------------
The primary aim is to examine changes in tumor perfusion, oxygen saturation, and tumor physiology before and following acute physical activity in breast cancer patients. The secondary aim is to examine changes in circulating tumor DNA (ctDNA) levels before and following acute physical activity in breast cancer patients. The tertiary aim is to explore changes in circulating exerkines (cytokines and growth factors altered by exercise) before and following acute physical activity in breast cancer patients.

Detailed Description
-----------------
The proposed study seeks to leverage acute exercise physiology as a tool to better understand multiple clinical and mechanistic issues in exercise oncology. An acute exercise bout causes functional changes such as increases in heart rate and stroke volume leading to increased cardiac output and increased systemic blood flow. These systemic effects also increase tumor blood flow (perfusion). Additionally, an increase in mean arterial pressure increases oxygen diffusion distance within the tumor. Further, acute exercise mobilizes NK cells, cytokine signaling, and a myriad of other molecular and cellular transducers of exercise. Our study of acute exercise physiology in breast cancer patients will address several significant knowledge gaps both clinically and mechanistically.

Official Title
-----------------
Women In Steady Exercise Research - Window of Opportunity for Exercise and Tumor Biology

Conditions
-----------------
Breast Cancer

Intervention / Treatment
-----------------
* Behavioral: Acute Exercise


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Newly diagnosed breast cancer patients Breast tumor is more than 2 cm (T2) With or without lymph node involvement (N0-3) With or without metastases (M0-M1) No initiation of neoadjuvant treatment Pre-surgical breast resection Exclusion Criteria: Current use of anticoagulants, including Vitamin K antagonists (e.g. Warfarin), Direct Oral Anticoagulants (DOACs) (e.g. Pradaxa, Eliquis, Xarelto, Bevyxxa, Savaysa), low molecular weight heparins (LMWH), Fragmin, Lovenox, heparin. Body weight <100 lbs Tis, T0, T1 Started neoadjuvant therapy Absolute contraindications for exercise stress testing by self-report: acute myocardial infarction (3-5 days) unstable angina uncontrolled arrhythmias causing symptoms or hemodynamic compromise syncope acute endocarditis acute myocarditis or pericarditis uncontrolled heart failure acute pulmonary embolus or pulmonary infarction thrombosis of lower extremities suspected dissecting aneurysm uncontrolled asthma pulmonary edema room air desaturation at rest ≤85% respiratory failure acute non-cardiopulmonary disorder that may affect exercise performance or be aggravated by exercise mental impairment leading to inability to cooperate decisional impairment Non-English speaking Pregnant women Children

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Acute exercise<br>Participants will be asked to walk or jog on a treadmill for a maximal exercise test. | Behavioral: Acute Exercise<br>* Participants will be asked to walk or jog on a treadmill for a maximal exercise test.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in total hemoglobin | Total hemoglobin will be quantified using photoacoustic imaging and the % difference will be determined 1) before cardiopulmonary exercise (CPET) (Time 0), 2) immediately after CPET (Time 1), 3) 30 min after CPET (Time 2) , and 4) 2 hours after CPET (Time 3). | baseline or before cardiopulmonary exercise (CPET), immediately after CPET (an average of 12 min following baseline), 30 min following CPET, and 2 hours following CPET | 
| Changes in oxy-hemoglobin | Oxy-hemoglobin will be quantified using photoacoustic imaging and the % difference will be determined at Time 0, Time 1, Time 2, and Time 3. | baseline or before cardiopulmonary exercise (CPET), immediately after CPET (an average of 12 min following baseline), 30 min following CPET, and 2 hours following CPET | 
| Changes in deoxy-hemoglobin | Deoxy-hemoglobin will be quantified using photoacoustic imaging and the % difference will be determined at Time 0, Time 1, Time 2, and Time 3. | baseline or before cardiopulmonary exercise (CPET), immediately after CPET (an average of 12 min following baseline), 30 min following CPET, and 2 hours following CPET | 
| Changes in oxygen saturation | Oxygen saturation will be quantified using photoacoustic imaging and the % difference will be determined at Time 0, Time 1, Time 2, and Time 3. | baseline or before cardiopulmonary exercise (CPET), immediately after CPET (an average of 12 min following baseline), 30 min following CPET, and 2 hours following CPET | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in ctDNA level | ctDNA level will be measured in blood and the % difference will be determined at Time 0, Time 1, Time 2, and Time 3. | baseline or before cardiopulmonary exercise (CPET), immediately after CPET (an average of 12 min following baseline), 30 min following CPET, and 2 hours following CPET | 
| Exerkine: TGF-β | TGF-β will be measured in blood and the % difference will be determined at Time 0, Time 1, Time 2, and Time 3. | baseline or before cardiopulmonary exercise (CPET), immediately after CPET (an average of 12 min following baseline), 30 min following CPET, and 2 hours following CPET | 
| Exerkine: VEGF-A | VEGF-A will be measured in blood and the % difference will be determined at Time 0, Time 1, Time 2, and Time 3. | baseline or before cardiopulmonary exercise (CPET), immediately after CPET (an average of 12 min following baseline), 30 min following CPET, and 2 hours following CPET | 
| Exerkine: S1P | S1P will be measured in blood and the % difference will be determined at Time 0, Time 1, Time 2, and Time 3. | baseline or before cardiopulmonary exercise (CPET), immediately after CPET (an average of 12 min following baseline), 30 min following CPET, and 2 hours following CPET | 
| Exerkine: TSP-1 | TSP-1 will be measured in blood and the % difference will be determined at Time 0, Time 1, Time 2, and Time 3. | baseline or before cardiopulmonary exercise (CPET), immediately after CPET (an average of 12 min following baseline), 30 min following CPET, and 2 hours following CPET | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
ctDNA, acute exercise, exerkines, tumor perfusion, oxygen saturation