There is growing recognition and acceptance of the integral role of exercise following a breast cancer diagnosis. This emerging dogma is based, in large part, on evidence from randomized trials indicating that exercise improves symptom control as well as observational data suggesting that regular exercise is associated with substantial reductions in cancer-specific and all-cause mortality in women following a breast cancer diagnosis. Prior to launching a large-scale RCT investigating the effects of exercise on disease outcome, it is first of crucial importance to gather informative pilot data to establish the safety and feasibility and potential efficacy of exercise training in women with metastatic disease undergoing chemotherapy. We propose a randomized phase II trial to assess the antitumor activity and toxicity of the addition of aerobic training to standard chemotherapeutic regimens relative to chemotherapy alone (plus attention-control) among 72 women with HER-2 negative metastatic breast cancer. This grant will have the following three specific aims: (1) to determine the feasibility and safety of supervised aerobic training among women undergoing chemotherapy for metastatic breast cancer, (2) to quantify the potential efficacy (and variation) of supervised aerobic training on changes in patient-reported outcomes and cardiopulmonary function, and (3) to explore the effects on biomarkers of breast cancer progression and mortality (i.e., inflammatory cytokines and growth factors). This will be the first study to investigate these questions. PUBLIC HEALT RELEVANCE: There is growing recognition and acceptance of the integral role of exercise following a diagnosis of early-stage breast cancer (BC). Despite these positive findings, no study to date has investigated the role of exercise among women diagnosed with advanced (metastatic) breast cancer (MBC). The strong evidence base in early-stage BC suggests that exercise may be an appropriate supportive intervention to improve functional capacity and symptom control in MBC. However, relative to studies in the early-stage setting, exercise trials in MBC pose a unique challenge with respect to disease severity and clinical prognosis, extent of comorbid disease, and prior and current treatment with aggressive combination cytotoxic and supportive care regimens. Thus, prior to launching a definitive RCT, it is first of critical importance to determine the feasibility, safety, and initial efficacy of exercise in this setting. To address this question, we propose a randomized phase II trial among 72 women undergoing chemotherapy for MBC.