This study is being done to look at the effect that different amounts of progressive exercise training has on risk factors associated with developing breast cancer. These risk factors include exercise capacity, body weight, and body composition, as well as the expression of certain genes and levels of inflammatory factors in your breast tissue.

The participant will be instructed to self-report the session information to ExOnc staff at or before their next scheduled visit. If the participant's next scheduled visit is greater than 72 hours following an unsupervised session, ExOnc staff may reach out to the participant to retrieve the session information. Unsupervised session details will be source documented by ExOnc staff.

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](streamdown:incomplete-link)

Women at High-Risk for Development of Breast Cancer