Exercise, Fitness and Tumor Profiling in Breast Cancer Patients

Study Overview
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Brief Summary
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This study is designed to find out how engaging in regular exercise (or not) alters the biology of breast tumors as well as the normal tissue (if available) surrounding the tumor. The investigators hope that findings from this initial study will guide the design of future studies to examine how changes in exercise alter breast tumor biology.

Official Title
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Integrative Profiling of Primary Breast Cancer on the Basis of Divergent Exercise Exposure

Conditions
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Breast Cancer

Intervention / Treatment
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* Behavioral: Harvard Health Professionals survey
* Other: Blood draw
* Other: CPET Procedures
* Other: stool sample
* Procedure: Research Tissue sampling


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cohort 1: Breast Cancer Patients Ages 21-80 years Female Histologically confirmed ER receptor positive (>1% staining), HER2 negative (FISH ratio <1.8), untreated operable breast cancer Stage I to II disease Scheduled for surgical resection by any type of mastectomy or lumpectomy at MSK Tumor size ≥1cm by preoperative imaging or physical examination Categorization into self-reported exercise history exposure classifications as follows: (1) exercising: ≥120 minutes of vigorous-intensity exercise/wk for the past 12 months, and (2) sedentary (non-exercising): ≤ 30 minutes of moderate-intensity exercise/week for the past months using the Harvard Health Professionals survey.(34) Ability to read and understand English Willing and able to comply with requirements of the protocol Cohort 2: High-Risk Patients Women at high-risk of breast cancer, as defined by one of the following: Cytologically confirmed atypical hyperplasia confirmed LCIS Being a carrier for BRCA1 and/or BRCA2 Predicted lifetime risk of breast cancer >20% based on family history Predicted 10-year risk of breast cancer of ≥2.31% Predicted 5-year risk of breast cancer ≥1.67% Aged 21-80 years old If a female of child-bearing potential, must not be pregnant or planning to become pregnant during the study. Women <50 years old of child-bearing potential must have a negative pregnancy test (urine HCG or serum) within 14 days of enrollment. Exclusion Criteria: Cohort 1: Received any form of neoadjuvant treatment Presence of any other concurrent, actively treated malignancy Presence of metastatic disease If performing a CPET, any of the following contraindications: Acute myocardial infarction within 3-5 days of any planned study procedures; Unstable angina Uncontrolled arrhythmia causing symptoms or hemodynamic compromise Recurrent syncope Active endocarditis Acute myocarditis or pericarditis Symptomatic severe aortic stenosis Uncontrolled heart failure Acute pulmonary embolus or pulmonary infarction within 3 months of any planned study procedures Thrombosis of lower extremities Suspected dissecting aneurysm Uncontrolled asthma Pulmonary edema Respiratory failure Acute non-cardiopulmonary disorders that may affect exercise performance or be aggravated by exercise (i.e., infection, renal failure, thyrotoxicosis). Mental impairment leading to inability to cooperate If performing a CPET, room air desaturation at rest ≤ 85% Any other condition or intercurrent illness that, in the opinion of the investigator, makes the participant a poor candidate for the study. Cohort 2: Use of any selective estrogen receptor modulator or aromatase inhibitor within 6 months of consent, including, but not limited to: tamoxifen, raloxifene, arzoxifene, acolbifene, anastrozole, exemestane, and letrozole. Enrollment on an interventional investigational study Bilateral breast implants History of any of the following: Invasive breast cancer DCIS Any current invasive cancer diagnosis Metastatic malignancy of any kind If performing a CPET, any of the following contraindications: Acute myocardial infarction within 3-5 days of any planned study procedures; Unstable angina Uncontrolled arrhythmia causing symptoms or hemodynamic compromise Recurrent syncope Active endocarditis Acute myocarditis or pericarditis Symptomatic severe aortic stenosis Uncontrolled heart failure Acute pulmonary embolus or pulmonary infarction within 3 months of any planned study procedures Thrombosis of lower extremities Suspected dissecting aneurysm Uncontrolled asthma Pulmonary edema Respiratory failure Acute non-cardiopulmonary disorders that may affect exercise performance or be aggravated by exercise (i.e., infection, renal failure, thyrotoxicosis). Mental impairment leading to inability to cooperate If performing a CPET, room air desaturation at rest ≤ 85% Any other condition or intercurrent illness that, in the opinion of the investigator, makes the participant a poor candidate for the core biopsy or the study.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Regular exercisers and non-exercising groups who have been diagnosed with breast cancer<br>There is no treatment on this study, it is a onetime assessment. exercisers: ≥120 minutes of vigorous-intensity aerobic exercise;There is no treatment on this study, it is a onetime assessment. non-exercisers: ≤ 30 minutes of moderate-intensity exercise per week. | Behavioral: Harvard Health Professionals survey<br>* Participants will be asked a series of questions (using a validated questionnaire) to assess self-reported exercise exposure over the past 12 months.<br>Other: Blood draw<br>* Participant will provide a blood sample<br>Other: CPET Procedures<br>* CPET with 12-lead ECG<br>Other: stool sample<br>* Research stool sample (within ±1 week of surgery), if possible<br>Procedure: Research Tissue sampling<br>* Sample of the tumor and normal breast tissue may be taken from the tissue removed during breast cancer surgery if there is enough tissue left over for research testing.<br>|
| Regular exercisers who are at high risk of developing breast cancer<br>≥120 minutes of vigorous-intensity aerobic exercise; | Behavioral: Harvard Health Professionals survey<br>* Participants will be asked a series of questions (using a validated questionnaire) to assess self-reported exercise exposure over the past 12 months.<br>Procedure: Research Tissue sampling<br>* Sample of the tumor and normal breast tissue may be taken from the tissue removed during breast cancer surgery if there is enough tissue left over for research testing.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| differences in DNA somatic mutational profile | Eight-μm-thick representative sections of the fresh-frozen sample will be microdissected with a needle under a stereomicroscope (Olympus SZ61), to ensure >70% of tumor cell content as previously described.(36) Matched germline DNA will be microdissected from adjacent normal breast tissue (if available) for each case; to avoid the possibility of morphologically appearing non-neoplastic cells harboring somatic mutations; we will prioritize the microdissection of stromal cells and avoid normal breast ducts and lobules. | 2 years | 
| differences in RNA sequencing | The initial analysis will focus on immune signatures (i.e., immune activation, as well as preexisting immune and related signatures) characterization using RNA-seq | 2 years |