High-Risk Breast Duct Epithelium
Breast cancer is the most common malignancy in women, occurring in over 180,000 women annually in the United States.
The vast majority of breast cancers originate in the single layer of epithelial cells that line the ductal/lobular system of the breast milk ducts. The premalignant changes which occur in the transformed epithelium are not well understood, however several cytologic or histologic changes have been identified which are associated with an increased risk for breast cancer, including ductal or lobular hyperplasia, hyperplasia with atypia, and lobular or ductal carcinoma in situ.
The identification of cytological or histological abnormalities in breast epithelial cells is an important component of risk assessment.
The primary objectives are:
To determine the incidence and nature of cytologic changes in ductal epithelial cells from the high risk breast, in specimens collected by breast duct lavage, and to determine if these cytologic findings are different from those of normal women not at increased risk for breast cancer.
To characterize by breast duct endoscopy, high risk breast ductal epithelium and architecture, and correlate these findings with the cytologic findings from above.
To determine what is the global gene expression pattern of high risk breast epithelial cells from the high risk breast, and does this differ from that of breast epithelial cells from normal women not at increased risk for breast cancer. The gene expression profile will be determined by cDNA microarray and validated by RT-PCR.
To determine by comparative genomic hybridization the gross genomic alterations present in high risk breast epithelial cells.
To determine the pattern of protein expression for selected proteins in the high risk epithelial cells using proteomics tissue lysate arrays.
To examine ductal epithelial cell preparations from both normal risk and high risk women for the presence of mammary stem cells.
Eligibility for high risk individuals will include:
Women of any age with a unilateral invasive or noninvasive (DCIS) breast cancer of epithelial origin.
Women without breast cancer, but with a Gail Index greater than 1.67%.
Women known to be BRCA1/2 mutation carriers.
Women with cytologic or histologic evidence of ductal hyperplasia, atypical ductal hyperplasia, or lobular carcinoma in situ.
Women may be either premenopausal or postmenopausal. Postmenopausal is defined by the absence of menstrual periods for at least 24 months.
Postmenopausal women who have previously undergone a hysterectomy without oophorectomy must have a serum FSH level of greater than 40 IU/ml, and a serum estradiol level of less than 40 pg/ml to document postmenopausal status.
Eligibility for normal volunteers will include:
Women who are premenopausal or postmenopausal with a Gail model risk index Less than 1.67%.
Women who have previously undergone a hysterectomy without oophorectomy must have a serum FSH level of greater than 40 IU/ml, and a serum estradiol level of less than 40 pg/ml to document postmenopausal status.
Both breasts must be free of any suspicious areas by physical examination and mammogram, and no past history of atypical hyperplasia, invasive or in situ carcinoma.
Both groups must have acceptable WBC and platelet counts.
Breast ductal epithelial cells will be collected by breast duct lavage from a.) the breast in women at increased risk for breast cancer, and b.) the breast of female normal volunteers who are not at increased risk for breast cancer.
Ductal epithelial cell specimens will be analyzed cytologically for the presence of hyperplasia, atypia, or in situ changes.
Breast duct endoscopy will be performed in breast cancer patients and in normal volunteers to determine ductal architectural changes associated with increased risk for breast cancer, and to provide correlation with cytologic studies.
The gene expression profile of normal and high risk ductal epithelial cells will be studied by cDNA microarray to determine changes in gene expression associated with increased risk for breast cancer.
Additional molecular profiling experiments which will be performed as lavage cells are available include Comparative Genomic Hybridization (CGH), proteomic tissue lysate arrays, and identification of mammary stem cells.
A total of 70 breast cancer patients and 40 normal volunteers will be studied, divided approximately evenly between premenopausal and postmenopausal women. After accruing the first 20 individuals for a given menstrual status, an analysis will be performed. If more than 5 patients yield less than or equal to 7000 ductal cells/lavage, then the trial will be re-evaluated prior to proceeding with additional enrollment....
|Official Title:||Characterization of High Risk Breast Duct Epithelium by Cytology, Breast Duct Endoscopy, and cDNA Gene Expression Profile|
|Study Start Date:||December 2001|
Please refer to this study by its ClinicalTrials.gov identifier: NCT00028340
|Contact: David N Danforth, M.D.||(301) firstname.lastname@example.org|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office (888) NCI-1937|
|Principal Investigator:||David N Danforth, M.D.||National Cancer Institute (NCI)|