Background: Intratumoral cryo combined with immune modulation generates a potent systemic anti-tumor immune response that might improve recurrence-free survival in ESBC. Cryo-mediated tumor destruction results in necrosis and immunogenic cell death which exposes dendritic cells (DC) to sufficient quantities of tumor antigens and inflammatory cytokines to induce their maturation and activation and elicit tumor specific T cell responses. To further amplify this immune response we use ipi, a human monoclonal antibody that blocks cytotoxic T lymphocyte antigen-4 (CTLA4). In preclinical murine models, the combination of cryo with CTLA4 blockade successfully mediates rejection of metastatic prostate cancer lesions and prevents growth of secondary tumors. We therefore hypothesize that this strategy could confer long-term immunity for pts with ESBC. In this study, we evaluate the safety of pre-op cryo and/or immune modulation with single dose ipi (at 10 mg/kg) in pts with ESBC. Methods: Pts are sequentially assigned to receive pre-op: cryo alone (Group A), ipi alone (B), or ipi with cryo (C). Cryo is administered 7-10 d prior to surgery. Ipi is administered 8-15 d prior to surgery (1-5 d prior to cryo). If at least 5/6 pts in each group proceed with surgery without delay, the regimen will be considered safe/tolerable.Primary aim: To evaluate the safety of pre-op cryo and/or ipi (10mg/kg) in pts with ESBC.Seconday aims: To characterize pre- and post-intervention radiographic and immunological (peripheral blood and tumor tissue) correlates. Eligibility: Pts ≥18y of age with operable ≥1.5 cm invasive ESBC, no history of autoimmune disease and planned mastectomy. Study status: As of January 25, 2013 7/7 pts were enrolled to Group A (expanded after 1 pt had suspected incomplete cryo) and 5/6 pts were enrolled to Group B. Enrollment to Group C will open when the pts in Group B meet the safety endpoint 30 d (+/-10 d) after surgery. Toxicity evaluation continues for 12 wks after ipi administration for Groups B and C. Clinical trial information: NCT01502592.