The purpose of this study is to study exercise in a novel population with indolent MBC (no progression on current therapy in prior 12 months and not receiving cytotoxic chemotherapy). The study team hypothesizes that delivering virtual, supervised, progressive intensity aerobic and resistance training exercise for 16 weeks in this population will significantly improve 1) cardiorespiratory fitness, functional status, and sarcopenia (low muscle mass), all established predictors of survival, and 2) patient- reported outcomes.

This is a randomized, two arm, single-center study designed to compare the effect of exercise versus usual care control on the clinical parameter of cardiorespiratory fitness, in patients with metastatic breast cancer with indolent disease biology over a 16-week period. This study will be enrolling up to 100 participants. Participants will be randomized 1:1 in blocks of 4 to the exercise intervention or usual care, stratified by frailty yes/no defined by baseline SPPB score ≤ 8 or > 8.

Primary Objective To compare the effect of a 16-week multimodality, virtually delivered exercise intervention on cardiorespiratory fitness measured by a modified Bruce ramp protocol treadmill test to usual care, in patients with indolent metastatic breast cancer.

Secondary Objectives

1. To compare the effect of exercise versus usual care on objective physical function measured by the short physical performance battery (SBBP)
2. To compare the effect of exercise versus usual care on subjective physical functioning measured by PROMIS-29 questionnaire
3. To compare the effect of exercise versus usual care on body composition, measured by visceral adiposity, lean muscle mass, and muscle density on CT scans obtained as standard of care using SliceOmatic software
4. To compare the effect of exercise versus usual care on objective physical activity measured by accelerometer wear
5. To compare the effect of exercise versus usual care on patient reported outcomes, including fatigue (BFI) and health related quality of life (PROMIS-29)
6. To determine the fidelity of the exercise intervention, measured by changes in measures of constructs of habit and intention administered by questionnaire
7. To describe patient uptake and adherence with the intervention, measured by proportion of approached patients who consent to the study, and proportion of assigned training sessions attended by patients randomized to the exercise arm.

Inclusion Criteria:

1. Age ≥ 18 years

2. Diagnosis of metastatic breast cancer

3. No progression of disease in the 12 months prior to screening per the treating investigator

   1. If participant has changed treatments in the prior 12 months for reasons other than progressive disease, they remain eligible
   2. Participants on no treatment or "no evidence of disease" but still with a diagnosis of metastatic breast cancer are eligible

4. ECOG performance status of 0-2

5. Ability to walk on a treadmill without assistive device.

6. Informed consent and authorization of the release of health information must be obtained according to institutional guidelines

7. Currently not meeting physical activity guidelines (defined as less than 150 minutes of moderate to vigorous exercise per week measured by the IPAQ questionnaire administered during screening)

8. Participants should have a cellular device compatible with iOS 15 or Android operating system 7.

Exclusion Criteria:

1. Receiving cytotoxic chemotherapy at any point in the prior 12 months.

   1. Participants receiving endocrine therapy are eligible.
   2. Participants receiving targeted therapy or antibody therapy are eligible (examples including trastuzumab, pertuzumab, TDM-1, trastuzumab deruxtecan, sacituzumab govetecan, immunotherapy, CDK4/6 inhibitors, olaparib, alpelisib, etc.)

2. Any condition precluding supervised exercise participation. A letter from a physician supporting participation can supersede this eligibility criteria.

   • NYHA class III or IV congestive heart failure
   • Uncontrolled angina
   • Myocardial infarction in the prior 12 months
   • Orthopedic surgery in the previous 3 months or plans for orthopedic surgery during the study period
   • Chronic uncontrolled pulmonary conditions such as uncontrolled asthma (symptoms > 2 days/week) or dyspnea requiring oxygen
   • Symptomatic peripheral vascular disease
   • Or any other comorbidity that would interfere with the ability to complete and comply with the protocol in the opinion of the investigator, including psychological illness
   • History of fragility fracture

3. Active, untreated brain metastases