Cell Lines From High-Risk Breast Tissue
Condition: Healthy
Study type: Observational

Summary: 
      Background:

        -  Many risk factors for breast cancer have been identified, including family history,
           endocrine background, changes in breast tissue, cancer in one breast, radiation
           exposure, obesity and others. There is a spectrum of tissue changes seen in cancerous
           and pre-cancerous breast tissue.

        -  A cell line is a collection of cells that are grown in the laboratory from an original
           tissue specimen. Cell lines developed from high-risk breast tissue allow researchers to
           perform metabolic and molecular studies of breast cells over time.

      Objective: To establish a repository (facility in which tissue samples can be preserved and
      stored for many years) of cell lines from high-risk breast tissue to allow researchers to
      learn more about changes in breast cells that may cause them to develop into breast cancer.

      Eligibility: Women between 20 and 80 years of age who:

        -  Have an increased risk of breast cancer because they are members of a high-risk breast
           or ovarian cancer family.

        -  Have had breast cancer in one or both breasts.

        -  Have had radiation for lymphoma before the age of 30.

        -  Have a mutation in a breast cancer susceptibility gene, but whose family history is not
           known.

        -  Are not at increased risk of breast cancer.

      Design:

        -  A small piece of breast tissue will be obtained from about 10 women without an
           identified risk of breast cancer and up to 100 women at high risk of developing breast
           cancer.

        -  Cell lines will be developed from each high-risk category.

        -  The cell lines and tissues will be used to establish a repository of high-risk breast
           cell lines and breast tissues that can be used to study how the cells develop into
           breast cancer.
    

Detailed description: 
      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.
    

Keywords: Surgery; Tissue Sample; Gene Expression Profiling; Tissue Array Gene Expression; Comparative Genomic Hybridization; Breast Cancer; Breast Cancer Risk; Breast