Dose-Response of Aerobic Training in Women at High-Risk for Development of Breast Cancer

Inclusion Criteria:

- Women at high-risk of breast cancer as defined by one of the following:

- Cytologically confirmed atypical hyperplasia

- Cytologically 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 who are of child-bearing potential must have a negative
pregnancy test (urine HCG or serum) within 14 days of enrollment.

- Must a negative mammogram or negative breast MRI within 1 year of protocol required
baseline core biopsy

- Clinical breast exam interpreted as benign (not suspicious for cancer) at MSK

- Performing less than or equal to 120 minutes of structured moderate-intensity or
strenuous-intensity exercise per week

- Able to complete an acceptable baseline CPET in the absence of high risk ECG findings
or other inappropriate response to exercise as determined by the investigator.

- Able to achieve an acceptable peek baseline CPET defined as by any of the following
criteria:

- achieving a plateau in oxygen consumption concurrent an with increase in power
output;

- a respiratory exchange ratio ≥ 1.10;

- attainment of maximal predicted heart rate (HRmax) (i.e., within 10 bpm of
age-predicted [HRmax = 220-Age[years]) Volitional exhaustion, as measured by a
rating of perceived exertion (RPE) ≥ 18 on the BORG scale.

Exclusion Criteria:

- Use of any selective estrogen receptor modulator or aromatase inhibitor within 6
months of randomization, including, but not limited to: (tamoxifen, raloxifene,
arzoxifene, acolbifene, anastrozole, exemestane, and letrozole)

- Enrollment on an interventional investigational study

- Bilateral breast implants

- Any newly identified breast abnormality requiring surgical excision

- History of any of the following:

- Invasive cancer diagnosis

- DCIS

- Flat epithelial atypia

- Any current invasive cancer diagnosis

- Metastatic malignancy of any kind

- Any other condition or intercurrent illness that in the opinion of the investigator
makes the subject a poor candidate for core biopsy or the trial

- Mental impairment leading to inability to cooperate.

- Room air desaturation at rest ≤85%

- Any of the following absolute contraindications to cardiopulmonary exercise testing
and/or aerobic training:

- 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); or