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
* 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