Abstract Background: Chemotherapy for breast cancer can have a detrimental effect on cardiorespiratory fitness. VO2max (maximal oxygen consumption measured during exercise) is a key predictor of cardiovascular risk and has been found to be lower in women with a history of breast cancer compared with healthy women. Chemotherapy is associated with a decrease in VO2max but these decreases may be attenuated with exercise training, such as resistance, aerobic and high-intensity interval training programs. Physical activity may reduce the risk of mortality for breast cancer patients, improve quality of life (QoL) and reduce weight. All gyms and fitness studios had to close due to the COVID-19 pandemic, and while some have re-opened, many patients are not comfortable returning to an exercise facility now and are incorporating virtual exercise into their routine. Prior studies have demonstrated the safety, feasibility and potential benefits of home-based exercise programs for breast cancer patients receiving chemotherapy. However, many of these programs are self-reported, which can create bias and to our knowledge, there is no existing data on the effect of home-based exercise programs for breast cancer patients receiving neoadjuvant chemotherapy. The goal of the STRENGTH Trial is to evaluate the effect of a 12-week virtual supervised exercise program in breast cancer patients receiving chemotherapy on cardiorespiratory fitness. Study Description: This is a single-center, prospective, single-arm study designed to evaluate the effect of a virtual supervised exercise training program in breast cancer patients receiving chemotherapy on cardiorespiratory fitness. All participants are assigned to a 12-week virtual supervised exercise program and asked to complete a total of 150 minutes of moderate intensity physical activity per week, as a combination of a weekly virtual personal training session and workout classes streamed from the Peloton®Digital platform (i.e. walking, running, cardio, yoga, strength training, and cycling classes). Due to the ongoing COVID-19 pandemic, cardiorespiratory fitness cannot be assessed using a cardiopulmonary exercise test. As such, the co-primary endpoints are resting blood pressure and heart rate and distance walked during a Six-Minute Walk Test (6MWT), which is measured at the start and completion of the 12-week supervised exercise program. Secondary endpoints are QoL as assessed by the Functional Assessment of Cancer Therapy - General (FACT-G) and symptom management assessment by the MD Anderson Symptom Inventory (MDASI). Several exploratory clinical endpoints will be collected including adherence to the program, type of fitness classes completed, and treatment toxicities. Eligibility Criteria: Patients aged ≥18 years with stage I to IV breast cancer who are planned to receive at least 12 weeks of chemotherapy of investigator’s choice are eligible for inclusion. Patients who have an ejection fraction on echocardiogram <40%, symptomatic heart failure, myocarditis, myocardial infarction, cerebrovascular accident, pulmonary embolism or COVID-19 infection within past 3 months, severe, uncorrected valvular disease, uncontrolled hypertension and/or uncontrolled arrhythmias are excluded. Statistical Methods: Continuous and categorical variables measured in this study will be summarized. The distributions of the data collected in the study participants from the 6MWT, FACT-G and MDASI will be evaluated. Based upon the findings, either paired t-tests or nonparametric Wilcoxon signed-rank tests will be performed to analyze the differences observed between the pre-exercise intervention data and the post-exercise intervention data. P values <= 0.05 will be considered statistically significant. . Accrual: At this time, 20 patients have enrolled out of a planned 30 participants. Citation Format: Eleonora Teplinsky, Amanda Podolski, Benita Burke, Kasey Bessada, Laura Klein, Moira Christoudias, Kariann Abbate. Supervised training exercise program during chemotherapy for breast cancer (STRENGTH) trial [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT2-13-01.