Cell Lines From High-Risk Breast Tissue

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.

Sex

Female

Minimum age

20 Years

Maximum age

80 Years

* INCLUSION CRITERIA:

To be eligible, women must have one of the following:

Women 20-80 years of age who have an increased risk of breast cancer because they are members of a high risk breast or ovarian cancer family. An Individual with a family history of verified breast and/or ovarian cancer is defined as including one of the following: 1) at least four cases of breast cancer. 2) Three cases of breast cancer and at least one case of ovarian cancer (two cases of ovarian cancer of which have to be first degree relatives). 3) Two cases of ovarian cancer in first degree relatives. High risk families may also include those with at least 4 cases of early onset (age less than 60) breast cancer or ovarian cancer (diagnosis at any age), or any family known to segregate a mutation in BRCA1 or another predisposing gene (i.e. BRCA2).

Women with a history of ipsilateral 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 or equal to 5 years since completing radiation therapy.

Normal women not at increased risk of breast cancer (Gail model Index of less than 1.50%) 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 tissues.

EXCLUSION CRITERIA:

Chemotherapy within 3 weeks prior to breast biopsy procedure.

Pregnancy,

White blood count less than 2000, platelet count less than 50,000.

Concurrent infection.

A history of bilateral whole breast radiation therapy.

A suspicious unbiopsied lesion by physical examination or mammography of the breast(s) which is being studied.

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• BACKGROUNDWidschwendter M, Berger J, Daxenbichler G, Muller-Holzner E, Widschwendter A, Mayr A, Marth C, Zeimet AG. Loss of retinoic acid receptor beta expression in breast cancer and morphologically normal adjacent tissue but not in the normal breast tissue distant from the cancer. Cancer Res. 1997 Oct 1;57(19):4158-61. PMID 9331065
• BACKGROUNDWoodcock DM, Linsenmeyer ME, Doherty JP, Warren WD. DNA methylation in the promoter region of the p16 (CDKN2/MTS-1/INK4A) gene in human breast tumours. Br J Cancer. 1999 Jan;79(2):251-6. doi: 10.1038/sj.bjc.6690041. PMID 9888465