Neo-adjuvant (pre-surgical) chemotherapy followed by mastectomy or lumpectomy and axillary node dissection has been successful in treating women with locally advanced breast cancer without distant metastases. Currently, decisions on how long to treat prior to surgery are hampered by the inability to accurately assess tumor response to therapy and the extent of residual viable tumor following treatment. In our preliminary patient studies, the Nuclear Medicine tracers [F-18]-fluorodeoxyglucose (FDG) and [Tc-99m]-Sestamibi (MIBI) have shown promise as accurate markers of tumor response. FDG is a PET tracer whose uptake reflects glucose metabolism, and it has been studied as a tracer of tumor response and viability for a variety of tumors, including preliminary investigations in breast cancer. MIBI is a more readily available single-photon tracer whose uptake most likely reflects a combination of tumor blood flow and metabolism. Our preliminary evaluation of MIBI to measure response to therapy has been encouraging. Our hypotheses are (1) that FDG or MIBI or both will provide accurate and timely measures of response to chemotherapy and the amount of residual viable tumor after therapy in patients with locally advanced breast cancer undergoing pre- surgical chemotherapy and (2) that the combination of MIBI and FDG together with O-15 water measurements of tumor blood flow will be able to characterize how breast tumors respond as they are treated and may be able to predict the likelihood of further response. We plan to (1) perform a clinical trial to determine the accuracy of FDG and MIBI for measuring response to therapy in comparison to the histopathological analysis of post-therapy surgical specimens and (2) compare relative MIBI and FDG uptake to O-15 water tumor blood flow measurements and immunocytochemistry markers of tumor vascularity and multi-drug resistance, as well as the ultimate degree of response. If successful, this work will result in the ability to perform measurements of tumor response that will significantly improve the treatment of patients with locally advanced breast cancer and will lead to insights into how these tumors respond when treated with neo-adjuvant chemotherapy.