In 2001, it is estimated that 192,200 women (and 1,500 men) in the United States will be diagnosed with breast cancer, and 40,600 will die from the disease. Of these new cases, approximately 30' or almost 60,000 will not contain the protein that binds estrogen, the so-called estrogen receptor (ER). The central focus of this Center of Excellence is the clinical problem of how to prevent and treat this type of breast cancer. Our overall idea is that these tumors represent one or more distinct breast cancer subtypes and that an understanding of the causal factors and critical pathways involved in the growth and malignant behavior of these tumors will ultimately lead to improvements in their prevention and treatment. We perceive this to be an important clinical problem, and our consumer advisors have reinforced this from their perspective. In fact, in his testimony before a Senate committee last month, the Director of the National Cancer Institute (NCI), Richard Klausner, highlighted the need to address this type of breast cancer as a priority. Thus, we feel this Center of Excellence addresses a major problem in breast cancer research and that its creation is timely. . Given the complexity of the problem, the combined efforts of investigators representing a wide array of different disciplines will be necessary to make significant progress. We have drawn investigators from across the Dana-Farber/Harvard Cancer Center (DF/HCC) member institutions and have enlisted important collaborators from both the Yale Medical School and the Whitehead Institute. In addition, this Department of Defense Breast Cancer Center of Excellence will be able to leverage the considerable infrastructure in place for breast cancer research across the DF/HCC and its NCI-funded Specialized Program of Research Excellence in Breast Cancer. These include an extensive tissue resource, the Breast Pathology Core, and the Clinical Research Information System (CRIS) database of breast cancer patients.