Acute Exercise Intervention in Breast Cancer Survivors

Current Inclusion Criteria (for Extension participants):

* Female
* History of Stage 0-IIIc breast cancer, diagnosed within the last 5 years
* Completed primary treatment at least 6 months ago
* Able to attend 2 clinic visits at the Fred Hutch Prevention Center for approximately 2.5 hours at a time
* Aged 36-75 years. Younger women will be excluded because a sizable proportion may remain premenopausal and will resume menstruation within 2 years of chemotherapy completion.
* Postmenopausal (no menstrual periods in the previous 12 months either naturally, or as a consequence of treatment)
* All race and ethnic groups are eligible for the study
* Able to perform all study requirements, including attendance at clinic visits and capable of responding to questionnaires and clinic and exercise facility instructions in English
* Willing to consent to release of medical records for their breast cancer diagnosis and treatment
* If a patient has received a cardiotoxic therapy (e.g., Adriamycin, Herceptin), clearance of their oncologist to participated in this study will be required.

Completed Inclusion Criteria (for participants enrolled prior to Extension portion of study):

* Resident in greater Seattle metropolitan area (King County), Pierce or Snohomish Counties
* Healthy
* Able to perform all study requirements, including attendance at clinic visits and capable of responding to questionnaires and clinic and exercise facility instructions in English
* Willing to be randomized
* Capable of providing informed consent

Current Exclusion Criteria (for Extension participants):

* Family history of breast cancer
* If known, BRCA 1/2 mutation carrier
* If known, Li-Fraumeni Syndrome
* Personal history of cancer other than breast: exceptions are non-melanoma skin cancer and cervical neoplasia (CIN)
* Serious health conditions including diabetes, renal disease (e.g., chronic kidney disease), liver disease (e.g., cirrhosis, chronic liver failure), chronic lung disease (COPD, moderate or severe persistent asthma), auto-immune disease requiring oral or inhaled medication, congestive heart failure, or other condition likely to interfere with ability to exercise at moderate levels and undergo biosampling, or likely to interfere with study outcomes.
* Fasting glucose fingerstick \>126 mg/dL
* Taking any medications to treat high blood sugar such as metformin
* Contraindications for exercise testing (29) including: recent (within 6 months) cardiac event (MI, pulmonary edema, myocarditis, pericarditis), unstable angina, uncontrolled arrhythmia, third degree heart block, left bundle branch block, acute congestive failure, recent (within 6 months) pulmonary/systemic embolus, severe electrolyte abnormality, deep vein thrombosis, uncontrolled hypertension (systolic \> 200, diastolic \> 100), orthostatic hypotension, moderate/severe aortic stenosis, uncontrolled arrhythmia, uncontrolled congestive heart failure, history of cardiac arrest or stroke, or as assessed by the physician assistant during the physical exam.
* History of clotting disorders
* Unable or unwilling to stop aspirin or NSAIDs for 48 hours before and after the procedure
* Allergy to anesthetics or local anesthetics
* Long term use of warfarin or similar medications
* Use of medications that could affect exercise ability, blood biomarkers, or muscle biomarkers, including weight loss medications, statins, oral beta-blockers, performance-enhancing drugs, metformin or other diabetic drug, and oral corticosteroids.
* Use of any sex hormones (estrogen, progesterone, testosterone or other androgens, for the previous 3 months) of any type including oral, creams, vaginal creams or inserts, patches, implants). Participants will be allowed to be on maintenance anti-estrogen therapy - e.g., tamoxifen, aromatase inhibitors
* Consumption of (on average) more than 2 alcoholic drinks per day
* Current use of any tobacco products including smoking, vaping, chew, nicotine patches
* Frequent marijuana use (\>1 per month)
* Current participation in another randomized controlled trial

Completed Exclusion Criteria (for participants enrolled prior to Extension portion of study):

* Pregnant in past 3 months
* Lactating
* Premenopausal women: irregular menstrual periods for the previous 6 months; no use of oral contraceptives for the previous 3 months, no use of hormone implants or intrauterine device (IUD) for in the previous year, no use of other sex hormones including testosterone or other androgens for the previous 3 months
* Postmenopausal women: no use of any sex hormones (estrogen, progesterone, testosterone or other androgens, for the previous 3 months) of any type including oral, creams, vaginal creams or inserts, patches, implants
* Current use of any tobacco products including smoking, vaping, chew, nicotine patches
* History of diabetes mellitus, or fasting glucose fingerstick ≥ 126 mg/dL
* Taking any medications to treat high blood sugar such as metformin
* Personal history of invasive or in situ breast cancer
* Personal history of cancer other than breast: exceptions are non-melanoma skin cancer and cervical neoplasia (CIN)
* ≥ 2 alcoholic drinks/day
* Contraindications to exercise
* Abnormalities on screening physical that contraindicate participation
* Contraindications for entry into a research exercise program: recent (within 6 months) myocardial infarction, pulmonary edema, myocarditis, pericarditis, unstable angina, pulmonary embolism, deep vein thrombosis, uncontrolled hypertension (systolic \> 200, diastolic \> 100), orthostatic hypotension, moderate/severe aortic stenosis, uncontrolled arrhythmia, uncontrolled congestive heart failure, left bundle branch block, history of cardiac arrest or stroke
* Frequent marijuana use (\> 1 per month)
* Alcohol or drug abuse, significant mental illness (as assessed by study staff impression)
* History of clotting disorders (muscle-biopsy sub study)
* Unable or unwilling to stop aspirin or nonsteroidal antiinflammatory drugs (NSAIDs) for 48 hours before and after the procedure (muscle-biopsy sub study)
* Allergy to anesthetics or local anesthetics (muscle-biopsy sub study)
* Long term use of warfarin or similar medications (muscle-biopsy sub study)