Researchers think that exercise may be able to prevent cancer from coming back by lowering ctDNA levels. The purpose of this study is to explore how aerobic exercise (exercise that stimulates and strengthens the heart and lungs and improves the body's use of oxygen) can reduce the level of ctDNA found in the blood. During the study, the highest level of exercise that is practical, is safe, and has positive effects on the body that may prevent the return of cancer (including a decrease in ctDNA levels) will be found. Each level of exercise tested will be a certain number of minutes each week. Once the best level of exercise is found, it will be tested further in a new group of participants. All participants in this study will have been previously treated for breast, prostate, or colorectal cancer.

Inclusion Criteria:

• Postsurgical diagnosis of patients with primary solid tumors at high-risk of relapse as defined by one of the following:

  ° High-risk primary solid tumor (e.g., colorectal, ovarian, non-small cell lung cancer) (colorectal cancer only for Phase 1a)

• Stage 3 or

• ctDNA positive

  ° High-risk breast cancer

• Residual invasive disease in the breast or the lymph nodes following completion of neoadjuvant chemotherapy (NACT),

• Estrogen receptor (ER), and/or progesterone receptor (PR) positive and HER2 negative,

• CPS-EG score ≥ 3,

• CPS-EG score ≥2 w ith ypN+, or

• Recurrence score ≥ 25

• No evidence of disease

• Age ≥ 18

• Interval of ≥ 1 month but ≤ 2 years following completion of all definitive adjuvant therapy

• Non-exercising (i.e., < 30 minutes of moderate and < 20 mins of vigorous exercise/wk), as assessed by remote activity and heart rate tracking for a 7-day period prior to study entry)

  ° If ≥ 30 minutes but less than 45 minutes of moderate exercise/week, or if ≥ 20 minutes but less than 30 minutes of vigorous exercise/week, patients may be eligible, at the discretion of the PI.

• Cleared for exercise participation as per screening clearance via PAR-Q+

• Willingness to comply with all study-related procedures

Exclusion Criteria:

• Enrollment onto any other interventional investigational study except interventions determined by the PI not to confound study outcomes
• Any other current diagnosis of invasive cancer of any kind
• Distant 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 study participation

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.