Ignite Creation Date:
2024-05-05 @ 11:24 AM
Last Modification Date:
2024-10-26 @ 9:06 AM
Study NCT ID:
NCT00028340
Status:
COMPLETED
Last Update Posted:
2023-01-10
First Post:
2001-12-21
Brief Title:
High-Risk Breast Duct Epithelium
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Characterization of High-Risk Breast Duct Epithelium by Cytology Breast Duct Endoscopy and cDNA Gene Expression Profile
Status:
COMPLETED
Status Verified Date:
2023-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Background
Breast cancer is the most common malignancy in women occurring in over 230000 women annually in the United States
The vast majority of breast cancers originate in the single layer of epithelial cells that line the ductallobular 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 167 percent or a cumulative lifetime risk greater than or equal to double the age- and race-matched general population risk
Women known to be BRCA12 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 IUml and a serum estradiol level of less than40 pgml to document postmenopausal status
Eligibility for normal volunteers will include
Women who are premenopausal or postmenopausal with a Gail model risk index less than 167 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 IUml and a serum estradiol level of less than 40 pgml 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
Breast cancer is the most common malignancy in women occurring in over 230000 women annually in the United States
The vast majority of breast cancers originate in the single layer of epithelial cells that line the ductallobular 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 167 percent or a cumulative lifetime risk greater than or equal to double the age- and race-matched general population risk
Women known to be BRCA12 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 IUml and a serum estradiol level of less than40 pgml to document postmenopausal status
Eligibility for normal volunteers will include
Women who are premenopausal or postmenopausal with a Gail model risk index less than 167 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 IUml and a serum estradiol level of less than 40 pgml 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 230000 women annually in the United States
The vast majority of breast cancers originate in the single layer of epithelial cells that line the ductallobular 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
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 167 percent or a cumulative lifetime risk greater than or equal to double the age- and race-matched general population risk
Women known to be BRCA12 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 IUmL and a serum estradiol level of 40 pgmL to document postmenopausal status
Eligibility for normal volunteers will include
Women who are premenopausal or postmenopausal with a Gail model risk index 167 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 40 IUmL and a serum estradiol level of 40 pgmL 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
Breast cancer is the most common malignancy in women occurring in over 230000 women annually in the United States
The vast majority of breast cancers originate in the single layer of epithelial cells that line the ductallobular 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
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 167 percent or a cumulative lifetime risk greater than or equal to double the age- and race-matched general population risk
Women known to be BRCA12 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 IUmL and a serum estradiol level of 40 pgmL to document postmenopausal status
Eligibility for normal volunteers will include
Women who are premenopausal or postmenopausal with a Gail model risk index 167 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 40 IUmL and a serum estradiol level of 40 pgmL 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 02-C-0077 | None | None | None |