High-Risk Breast Duct Epithelium

NCT00028340 | Completed

• 2 other identifiers: 02007702-C-0077
• Study Type: observational
• Target: 156
• Locations: 1 country
• Sites: 1

Brief Summary

Background:

• Breast cancer is the most common malignancy in women, occurring in over 230,000 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. Objective: 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 ductal lavage, and to determine if these cytologic findings are different from those of female normal volunteers 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 referenced in above bullet.
• 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 female normal volunteersnot at increased risk for breast cancer. The gene expression profile will be determined by cDNA microarray and validated by RT-PCR. Eligibility: Eligibility for high risk individuals will include:
• Women 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 percent, or a cumulative lifetime risk greater than or equal to double the age- and race-matched general population risk.
• Women known to be BRCA1/2 or other hereditary genes 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 12 months.
• Postmenopausal women who have previously undergone a hysterectomy without oophorectomy must have a serum FSH level of \> 40 IU/ml, and a serum estradiol level of less than40 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 percent, and without a cumulative lifetime risk greater than or equal to double the age- and racematched general population risk.
• Women who have previously undergone a hysterectomy without oophorectomy must have a serum FSH level of \>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, for women over 30 years of age by mammogram. There must be no history of atypical hyperplasia, invasive or in situ carcinoma. Both groups must have acceptable white blood cell and platelet counts. Design: Breast ductal epithelial cells will be collected by breast ductal 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 with cytologic atypia on ductal lavage to determine ductal architectural changes associated with increased risk for breast cancer, and to provide correlation with cytologic atypia. 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 DNA whole exome sequencing, Comparative Genomic Hybridization (CGH), proteomic tissue lysate arrays, and identification of mammary stem cells. A total of 104 high-risk subjects and 110 normal volunteers will be studied, divided approximately evenly between premenopausal and postmenopausal women....

Conditions

Breast Cancer

Keywords

Breast Cancer; Natural History

Outcome Measures

Primary Outcomes (3)

• Determine the incidence and nature of cytologic changes in ductal epithelial cells from the high-risk breast.

  Using specimens collected by breast ductal lavage, and determine if these cytologic findings are different from those of normal women not at increased risk for breast cancer.

  25 years

• Determine the global gene expression pattern of high-risk breast epithelial cells from the high-risk breast.

  Determine if gene expression pattern differs from that of breast epithelial cells from female normal volunteers not at increased risk for breast cancer. Gene expression profile will be determined by cDNA microarray and validated by RT-PCR.

  25 years

• Characterize high-risk breast ductal epithelium and architecture.

  Characterize by breast duct endoscopy, and correlate these findings with the cytologic findings.

  25 years

Secondary Outcomes (4)

• Examine ductal epithelial cell preparations for the presence of mammary stem cells.

  25 years

• Determine the pattern of protein expression for selected proteins in the high-risk epithelial cells.

  25 years

• Determine the gross genomic alterations present in high-risk breast epithelial cells.

  25 years

• Determine the DNA mutational pattern of breast epithelium from women at high risk for breast cancer.

  25 years

Study Arms (2)

1/Breast Cancer and High-Risk Patients

Pre- or postmenopausal women who have or have previously had invasive or noninvasive breast cancer of epithelial origin, or women without breast cancer but at an increased risk of breast cancer.

2/Normal Volunteers

Pre- or postmenopausal women who are not at an increased risk for breast cancer.

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Pre- or postmenopausal women who have or have previously had invasive or noninvasive breast cancer of epithelial origin, or women without breast cancer but at an increased risk of breast cancer. Pre- or postmenopausal women who are not at an increased risk for breast cancer.

You may qualify if:

• Age greater than or equal to 18 years and less than or equal to 74 years.
• Women 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 percent, or a cumulative lifetime risk greater than or equal to double the age- and race-matched general population risk.
• Women known to be BRCA1/2 or other hereditary genes mutation carriers.
• Women with cytologic or histologic evidence of ductal hyperplasia, atypical ductal hyperplasia, or LCISl
• Women may be either premenopausal or postmenopausal. Postmenopausal is defined by the absence of menstrual periods for at least 12 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.
• Breast cancer may be invasive or noninvasive, and in the past or the present.
• The contralateral breast of women with breast cancer, or the normal breast of high-risk subjects, must be free of any suspicious areas by physical examination and mammogram, and without a history of invasive ductal or in situ ductal carcinoma. History of atypia or LCIS on a previous biopsy is acceptable.
• Women who are from a family with heritable breast cancer with a known deleterious BRCA1/2 or other hereditary genes mutation, who themselves have been tested and to not carry this mutation. These women are not at increased risk for breast cancer due to the familial mutation and are eligible to participate as normal volunteers.
• WBC greater than 2,500.
• Platelets greater than 50,000.
• Age greater than or equal to 18 years and less than or equal to 74 years.
• Women who are premenopausal or postmenopausal with a Gail model risk index less than 1.67 percent, and without a cumulative lifetime risk greater than or equal to double the age- and race-matched general population risk.
• 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.

You may not qualify if:

• Contralateral breast prosthesis
• Pregnancy
• History of radiation therapy to the contralateral breast
• Lactating breasts
• Chemotherapy within the past 1 month
• Current antiestrogen therapy
• Current hormonal replacement therapy or oral contraceptives
• Concurrent infection
• Previous contralateral major duct excision
• Bilateral breast prosthesis
• Pregnancy
• Lactating breasts
• Current antiestrogen therapy
• Current hormonal replacement therapy or oral contraceptives
• Concurrent infection

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Fisher B, Costantino J, Redmond C, Fisher E, Margolese R, Dimitrov N, Wolmark N, Wickerham DL, Deutsch M, Ore L, et al. Lumpectomy compared with lumpectomy and radiation therapy for the treatment of intraductal breast cancer. N Engl J Med. 1993 Jun 3;328(22):1581-6. doi: 10.1056/NEJM199306033282201.

  PMID: 8292119 BACKGROUND

• Greenlee RT, Murray T, Bolden S, Wingo PA. Cancer statistics, 2000. CA Cancer J Clin. 2000 Jan-Feb;50(1):7-33. doi: 10.3322/canjclin.50.1.7.

  PMID: 10735013 BACKGROUND

• Fisher B, Dignam J, Wolmark N, Wickerham DL, Fisher ER, Mamounas E, Smith R, Begovic M, Dimitrov NV, Margolese RG, Kardinal CG, Kavanah MT, Fehrenbacher L, Oishi RH. Tamoxifen in treatment of intraductal breast cancer: National Surgical Adjuvant Breast and Bowel Project B-24 randomised controlled trial. Lancet. 1999 Jun 12;353(9169):1993-2000. doi: 10.1016/S0140-6736(99)05036-9.

  PMID: 10376613 BACKGROUND

• Danforth DN, Filie AC, Warner AC, Wright GW, Sun Z, Ried T, McGowan CT, Prindiville SA. Characteristics of Breast Ducts in Normal-Risk and High-risk Women and Their Relationship to Ductal Cytologic Atypia. Cancer Prev Res (Phila). 2020 Dec;13(12):1027-1036. doi: 10.1158/1940-6207.CAPR-19-0305. Epub 2020 Aug 4.

  PMID: 32753377 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• David N Danforth, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 21, 2001
• First Posted: December 24, 2001
• Study Start: February 20, 2003
• Primary Completion: December 16, 2022
• Study Completion: December 16, 2022
• Last Updated: January 10, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data will be available during the study and indefinitely.@@@@@@Genomic data will be available once genomic data are uploaded per protocol GDS plan for as long as database is active.
• Access Criteria: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI. @@@@@@Genomic data will be made available via dbGaP through requests to the data custodians.

Locations

US (1)