Cell Lines From High-Risk Breast Tissue

Background: The NCI Surgery Branch Multiple risk factors for breast cancer have been identified, including family history, endocrine background, histologic changes in breast tissue, cancer in one breast, radiation exposure, obesity, and others. The histologic phenotypes of breast carcinogenesis include a spectrum of changes, beginning with normal appearing breast epithelium, progressing to hyperplasia, atypical hyperplasia, in situ carcinoma, and finally invasive carcinoma. Our present knowledge of high risk breast tissue is based on the study of a variety of cellular sample types, which include fine needle aspirates, nipple aspirate fluid, core needle biopsies, and breast tissue from mastectomy or segmentectomy specimens. Valid preclinical models are needed which utilize homogenous human cellular material which can be studied over time in large quantities. A model which may be ideally suited to the metabolic and molecular studies of breast epithelial cells is an in vitro cell line model developed from high risk breast tissue. In this study normal breast tissue will be acquired from each of the high risk sites for breast cancer in the breast. These tissues will be used to develop breast epithelial cell lines for in vitro studies, and to establish a high risk cell line and tissue repository. Objectives: To acquire normal breast tissue from each of the high risk sites for breast cancer in the breast. To develop breast epithelial cell lines from the normal high risk breast tissue from each of the major high risk sites. To establish a repository of high risk breast epithelial cell lines and high risk normal breast tissue which can be used as a resource for pilot studies at NIH and other participating centers to characterize high risk breast epithelial cells Eligibility: Women age 20 - 80 years who have an increased risk of breast cancer because they are members of a high risk breast or ovarian cancer family. Women with a history of ipselateral breast cancer, either invasive or in situ, and a normal contralateral breast by mammography (within the past 12 months) and a normal physical examination of the contralateral breast and adjacent lymph node bearing areas, or be undergoing prophylactic mastectomy. Women without breast cancer but with a Gail model estimate of 5-year risk of breast cancer of 1.67 percent or higher. Women with bilateral breast cancer (invasive or in situ) who have not received whole breast irradiation to both breasts. Women with a previous history of mediastinal irradiation for lymphoma before the age of 30 and who are now greater than 5 years since completing radiation therapy. Normal women not at increased risk of breast cancer (Gail model Index of less than 1.50 percent) and without abnormal findings in the breast by physical examination and mammography to serve as normal control tissue. Women with a mutation in a breast cancer susceptibility gene, but whose family history is not known. Absence of significant cardiac, hepatic or renal disease, which, in the opinion of the PI, is likely to cause metabolic changes in the breast tissue. Design: A tissue acquisition in which Normal breast tissue will be collected from women at high risk of breast cancer at NIH and at other institutions as well. Centers collecting tissue for this protocol must have IRB approval for this study and an IRB approved Informed Consent. All breast tissue will be obtained from surgical specimens acquired as part of planned surgical procedures. Short-term cell lines will be developed from this tissue and confirmed cytologically and by expression of cytokeratins. Multiple cell lines from each of the high risk categories will be developed. These cell lines and the respective tissues will be used to establish a repository of high risk breast epithelial cell lines and high risk breast tissues which can be used to further define the carinogenic pathway for breast cancer. Early passages of these cell cultures and the respective normal breast tissue will be stored for future studies. 100 patients will be enrolled over a period of 5 years.