This study is being done to answer the following question: Will aerobic exercise (exercise that stimulates and strengthens the heart and lungs, and improves the body's use of oxygen) change the biomarkers (signs of disease) found in the blood?

Inclusion Criteria:

Cohort 1: CH

• CH called by MSK practices as documented by an MSK physician

• Age ≥18 yrs

• Completion of all anticancer therapy

• High risk of cardiovascular disease defined by presence of at least one of the following:

  • Age ≥60
  • Prior treatment with chemotherapy
  • Prior left-sided breast and/or chest wall radiotherapy
  • Currently receiving or previously received androgen deprivation therapy Prior bone marrow transplant
  • History of smoking
  • Currently treated for one or more cardiovascular risk factors (i.e., hypertension, diabetes, hyperlipidemia)

• Performing less than 150 minutes of structured moderate-intensity or strenuous-intensity exercise per week, as evaluated by self-report

• Willingness to comply with all study-related procedures

Cohort 2: Solid Tumor

• Patients at risk of harboring circulating tumor DNA as defined by one of the following:

  • Histologically confirmed stage III (i.e., high risk of recurrence) colorectal cancer within 2 years of completion of all adjuvant therapy.
  • Histologically confirmed stage III breast cancer with residual disease after neoadjuvant therapy and within 12 months of completing (neo)adjuvant chemotherapy
  • Patients with metastatic breast cancer and radiographic stable disease or NED for ≥6 months and not currently receiving chemotherapy (endocrine therapy and anti-HER2 antibodies allowed)

• Age ≥ 18 yrs

• Performing less than 150 minutes of structured moderate-intensity or strenuous-intensity exercise per week, as evaluated by self-report

• Willingness to comply with all study-related procedures

Cohort 3: Active Surveillance

• Men with histologically confirmed localized prostate cancer undergoing active surveillance
• Age ≥ 18 yrs
• Performing less than 15 minutes of structured moderate-intensity or strenuous-intensity exercise per week, as evaluated by self-report
• Willingness to comply with all study-related procedures
• Cleared for exercise participation as per pre-screening clearance via PAR-Q+

Cohort 4: Lynch Syndrome

• Age ≥18 yrs
• Hereditary colorectal cancer syndrome, specifically Lynch syndrome, defined by the presence of a deleterious germline mutation in the MLH1, MSH2, MSH6, PMS2 or EPCAM genes
• Have a portion of the distal colon or rectosigmoid intact to enable collection of normal mucosa biopsies
• Performing less than 150 minutes of structured moderate-intensity or strenuous-intensity exercise per week, as evaluated by self-report
• Willingness to comply with all study-related procedures
• Cleared for exercise participation as per pre-screening clearance via PAR-Q+

Cohort 5: EDD Phase 0a

• Age ≥18 yrs
• Receiving investigational agent under an EDD protocol for at least 2 months.
• Performing less than 150 minutes of structured moderate-intensity or strenuous-intensity exercise per week, as evaluated by self-report
• Willingness to comply with all study-related procedures
• Cleared for exercise participation as per pre-screening clearance via PAR-Q+

Phase 0b

• Age ≥18 yrs
• Newly Within 3 months of initiating investigational agent on an EDD Service protocol
• Performing less than 150 minutes of structured moderate-intensity or strenuous-intensity exercise per week, as evaluated by self-report
• Willingness to comply with all study-related procedures
• Cleared for exercise participation as per pre-screening clearance via PAR-Q+

Exclusion Criteria:

• Concurrent use of any form of antitumor therapy (endocrine therapy and anti-HER2 antibodies allowed)

• Enrollment onto any other interventional investigational study except interventions determined by the PI not to confound study outcomes (does not apply to Cohort 5: EDD)

• Any other condition or intercurrent illness that, in the opinion of the investigator, makes the subject a poor candidate for study participation.

• Mental impairment leading to inability to cooperate

• Any of the following contraindications to cardiopulmonary exercise testing (Cohorts 1 and 2 only):

  1. Acute myocardial infarction within 3-5 days of any planned study procedures;
  2. Unstable angina
  3. Uncontrolled arrhythmia causing symptoms or hemodynamic compromise
  4. Recurrent syncope
  5. Active endocarditis
  6. Acute myocarditis or pericarditis
  7. Symptomatic severe aortic stenosis
  8. Uncontrolled heart failure
  9. Acute pulmonary embolus or pulmonary infarction within 3 months of any planned study procedures
  10. Thrombosis of lower extremities within 3 months of any planned study procedures
  11. Suspected dissecting aneurysm
  12. Uncontrolled asthma
  13. Pulmonary edema
  14. Respiratory failure
  15. Acute non-cardiopulmonary disorders that may affect exercise performance

• Room air desaturation at rest ≤ 85% (Cohorts 1 and 2 only)

Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

For cohort 3 only. Men with histologically-confirmed localized prostate cancer undergoing active surveillance. Both patients and investigators will be fully blinded to the ctDNA status of patients during study participation.