Supportive Tailored Exercise Program for Survivors of Breast Cancer (STEPS-BC) - PROJECT SUMMARY Cardiovascular (CV) events after receipt of potentially cardiotoxic chemotherapy are emerging as the leading causes of morbidity and mortality for survivors of breast cancer (BC), the most common cancer in North American women. The objective of our proposal is to test whether a tailored exercise intervention that commences and continues throughout receipt of adjuvant chemotherapy can attenuate physical inactivity and fatigue, and preserve exercise capacity, left ventricular (LV) function, and health-related quality of life (HRQOL). We showed feasibility of our proposed intervention and performance of the outcome measures in R21CA226960 (Section 3.C.2). We now propose a pragmatic, multicenter, randomized controlled trial of a home-based physical activity intervention plus a healthy living intervention (HLI), versus HLI alone, in 150 women receiving anthracycline-based chemotherapy for BC, to preserve exercise capacity, LV function, and HRQOL, and reduce fatigue. Novel features of this proposal include: 1) Performance of physical activity during receipt of cancer treatment where exercise intolerance originates. 2) Creation of patient communities that enable cancer patients to support one another during treatment. 3) Delivery of aerobic and strength activities suited to one's individual lifestyle in the home guided by instruction from a central location, provided by exercise and behavioral specialists experienced in working with immunocompromised individuals or those with other pre-existing activity limitations. 4) Use of newly developed magnetic resonance and cardiopulmonary exercise testing methods to measure components (e.g., LV function and myocardial tissue characteristics) that contribute to peak oxygen consumption (a measure of maximal exercise capacity). This new information will provide mechanistic insight into how physical activity during cancer treatment helps preserve exercise capacity. 5) Assessment of physical activity, sedentary behavior, and exercise capacity to help to unravel associations among physical activity, HRQOL, and fatigue in cancer patients. 6) Measurement of systemic inflammation and LV myocardial fibrosis – both implicated in cancer treatment- associated CV dysfunction and modifiable through programs incorporating activity and exercise. 7) The first rigorous study of how dietary fatty acid intake affects exercise capacity among patients receiving treatment for breast cancer. We will partner with the Wake Forest NCI Community Oncology Research Program Research Base network in a novel and cost-effective collaboration. Ultimately, increasing physical activity during chemotherapy may lead to improved long-term outcomes for those with breast and other cancers, and establish a new paradigm for more effective and patient-centered care.