The Medical Breast Cancer Section has been investigating new therapeutic strategies for the treatment of breast cancer. These clinical trials have focused mainly on locally advanced breast cancer and metastatic disease; however, the therapeutic strategies developed in these advanced stages have recently been taken forward into early stage disease. The three major areas of clinical investigation over the past year have included: 1) overcoming drug resistance with dose intensive therapies; 2) the study of hematopoietic growth factors with intensive chemotherapy; and 3) new agents for breast cancer. Laboratory investigations of the breast cancer tissue obtained from patients are conducted in conjunction with the clinical trials as described in the following subprojects. Future plans include the further development of highly dose intensive chemotherapy regimens in conjunction with peripheral blood stem cells autografts. Another approach will involve the continuation of the study of hemopoietic growth factors including interleukin-3 (IL-3) in combination with GM-CSF. A new strategy that will be developed and initiated in the coming year involves Phase I trials of radiolabelled monoclonal antibodies against breast cancer antigens. We also plan to continue our work with taxol and adriamycin, using this regimen as induction therapy for patients with metastatic disease. We will also develop a new treatment regimen combining tamoxifen, 4-HPR and alpha interferon. These three agents have demonstrated synergistic activity up against breast cancer through their induction of growth suppressing factors. Lastly, the Medical Breast Cancer Section will move over the next year to conduct gene therapy trials in which the mdr-1 gene is inserted into peripheral blood stem cells. Reconstitution of patients' bone marrows with these genetically altered stem cells will thereby allow us to study the administration of high dose mdr-1-associated chemotherapy agents.