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High-Risk Breast Duct Epithelium

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ClinicalTrials.gov Identifier: NCT00028340
Recruitment Status : Recruiting
First Posted : December 24, 2001
Last Update Posted : February 6, 2020
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Tracking Information
First Submitted Date December 21, 2001
First Posted Date December 24, 2001
Last Update Posted Date February 6, 2020
Actual Study Start Date February 20, 2003
Primary Completion Date Not Provided
Current Primary Outcome Measures
 (submitted: August 1, 2018)
  • Determine the incidence and nature of cytologic changes in ductal epithelial cells from the high-risk breast. [ Time Frame: 20 years ]
    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.
  • Characterize high-risk breast ductal epithelium and architecture. [ Time Frame: 20 years ]
    Characterize by breast duct endoscopy, and correlate these findings with the cytologic findings.
  • Determine the global gene expression pattern of high- risk breast epithelial cells from the high-risk breast. [ Time Frame: 20 years ]
    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.
Original Primary Outcome Measures Not Provided
Change History Complete list of historical versions of study NCT00028340 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures
 (submitted: August 1, 2018)
  • Determine the DNA mutational pattern of breast epithelium from women at high risk for breast cancer. [ Time Frame: 20 years ]
    Using DNA whole exome sequencing.
  • Examine ductal epithelial cell preparations for the presence of mammary stem cells. [ Time Frame: 20 years ]
    From both women at high risk and from women not at high risk for breast cancer.
  • Determine the gross genomic alterations present in high-risk breast epithelial cells. [ Time Frame: 20 years ]
    Using comparative genomic hybridization.
  • Determine the pattern of protein expression for selected proteins in the high-risk epithelial cells. [ Time Frame: 20 years ]
    Using proteomics tissue lysate arrays.
Original Secondary Outcome Measures Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title High-Risk Breast Duct Epithelium
Official Title Characterization of High Risk Breast Duct Epithelium by Cytology, Breast Duct Endoscopy, and cDNA Gene Expression Profile
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.

Detailed Description

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 volunteers not 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.

Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
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.
Condition Breast Cancer
Intervention Not Provided
Study Groups/Cohorts
  • 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.
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: July 3, 2019)
214
Original Enrollment
 (submitted: June 23, 2005)
110
Study Completion Date Not Provided
Primary Completion Date Not Provided
Eligibility Criteria
  • INCLUSION CRITERIA:

Inclusion Criteria for Breast Cancer and High-Risk Patients:

  • 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.
  • Inclusion Criteria for Normal Volunteers:
  • 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.
    • 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.
    • WBC greater than 2,500.
    • Platelets greater than 50,000.

EXCLUSION CRITERIA:

  • Exclusion Criteria for Breast Cancer Patients:

    • 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
  • Exclusion Criteria for High-Risk Paitents:

    • Bilateral breast prosthesis
    • Pregnancy
    • Lactating breasts
    • Current antiestrogen therapy
    • Current hormonal replacement therapy or oral contraceptives
    • Concurrent infection
    • Previous bilateral major duct excision
    • History of therapeutic mediastinal radiation
  • Exclusion Criteria for Normal Volunteers:

    • Bilateral breast prosthesis
    • Pregnancy
    • Lactating breasts
    • Current antiestrogen therapy
    • Current hormonal replacement therapy or oral contraceptives
    • Concurrent infection
    • Previous bilateral major duct excision
    • History of therapeutic mediastinal radiation
Sex/Gender
Sexes Eligible for Study: Female
Ages 18 Years to 74 Years   (Adult, Older Adult)
Accepts Healthy Volunteers Yes
Contacts
Contact: David N Danforth, M.D. (240) 760-6213 danforth@pop.nci.nih.gov
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT00028340
Other Study ID Numbers 020077
02-C-0077
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
Study Sponsor National Cancer Institute (NCI)
Collaborators Not Provided
Investigators
Principal Investigator: David N Danforth, M.D. National Cancer Institute (NCI)
PRS Account National Institutes of Health Clinical Center (CC)
Verification Date January 8, 2020