Fresolimumab and Radiotherapy in Metastatic Breast Cancer

Inclusion Criteria: * Biopsy-proven breast cancer, metastatic (persistent or recurrent). * Failed ≥1 line of therapy (endocrine or chemotherapy) for metastatic disease. * Min. 3 distinct metastatic sites, at least one measurable lesion which is at least 1 cm or larger in largest diameter. * Must be ≥4 weeks since all of the following treatments (recovered from toxicity of prior treatment to ≤Grade 1, excluding alopecia): * major surgery; * radiotherapy; * chemotherapy (≥6 weeks since therapy if a nitrosourea, mitomycin, or monoclonal antibodies such as bevacizumab); * immunotherapy; * biotherapy/targeted therapies. * \>18 years of age. * Life expectancy \>6 months. * Eastern Cooperative Oncology Group (ECOG) status 0 or 1. * Adequate organ function including: * Hemoglobin ≥10.0g/dL, absolute neutrophil count (ANC) ≥1,500/mm3, and platelets ≥100,000/mm3. * Hepatic: Serum total bilirubin ≤1.5x upper limit of normal (ULN) (Patients with Gilbert's Disease may be included if total bilirubin is ≤3.0mg/dL), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) ≤2.5xULN. If patient has known liver metastases, ALT and/or AST ≤5xULN are allowed. * Renal: creatinine clearance ≥60mL/min. * Prothrombin (PT) and partial thromboplastin times (PTT) \<ULN. * Negative for hepatitis viruses B and C unless consistent with prior vaccination or prior infection with full recovery. * Patients of childbearing potential must agree to use effective contraception while on study, and for ≥3 months after last treatment. * Understand and sign written informed consent document. No consent by durable power of attorney. Exclusion Criteria: * Second malignancy - unless following curative intent therapy, has been disease free for ≥2 years with probability of recurrence \<5%. Curatively treated early-stage squamous cell carcinoma of the skin, basal cell carcinoma of the skin, or cervical intraepithelial neoplasia (CIN) are allowed. * Concurrent cancer therapy. * Uncontrolled central nervous system (CNS) metastases, meningeal carcinomatosis, malignant seizures, or disease that causes or threatens neurologic compromise (e.g. unstable vertebral metastases). * History of ascites or pleural effusions, unless successfully treated. * Organ transplant, including allogeneic bone marrow transplant. * Immunosuppressive therapy including: * Systemic corticosteroid therapy, including replacement therapy for hypoadrenalism. Inhaled or topical corticosteroids are allowed (if therapy is \<5 days and is limited to systemic steroids as antiemetics); * Cyclosporine A, tacrolimus, or sirolimus. * Investigational agents within 4 weeks prior to study enrollment (≥6 weeks if treatment was long-acting agent such as monoclonal antibody). * Significant or uncontrolled medical illness, e.g. congestive heart failure (CHF), myocardial infarction, symptomatic coronary artery disease, significant ventricular arrhythmias within the last 6 months, or significant pulmonary dysfunction. Patients with remote history of asthma or active mild asthma may participate. * Active infection, including unexplained fever (\>38.5°C). * Systemic autoimmune disease (e.g. systemic lupus erythematosus, active rheumatoid arthritis). * Known allergy to any component of GC1008. * Active thrombophlebitis, thromboembolism, hypercoagulability states, bleeding, or anti-coagulation therapy (including anti platelet agents i.e. aspirin, clopidogrel, ticlopidine, dipyridamole, other agents inducing long-acting platelet dysfunction). Patients with history of deep venous thrombosis are allowed if treated, completely resolved, and no treatment for \>4months. * Calcium \>11.0mg/dL (2.75mmol/L) unresponsive or uncontrolled in response to standard therapy (e.g. bisphosphonates). * Patients who, in the opinion of the Investigator, have significant medical or psychosocial problems, including, but not limited to: * Other serious non-malignancy-associated conditions that may be expected to limit life expectancy or significantly increase the risk of SAEs; * Conditions, psychiatric, substance abuse, or other, that, in the opinion of the Investigator, would preclude informed consent, consistent follow-up, or compliance with any aspect of the study; * Pregnant or nursing women.