Breast Cancer Clinical Trial in Bethesda MD
NCT00028340
| Observational
This study has recruited 156 Participants
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....
Details for the 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.
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:
<br />
<br /> - Breast cancer is the most common malignancy in women, occurring in over 230,000 women
<br /> annually in the United States.
<br />
<br /> - The vast majority of breast cancers originate in the single layer of epithelial cells
<br /> that line the ductal/lobular system of the breast milk ducts. The premalignant changes
<br /> which occur in the transformed epithelium are not well understood, however several
<br /> cytologic or histologic changes have been identified which are associated with an
<br /> increased risk for breast cancer, including ductal or lobular hyperplasia, hyperplasia
<br /> with atypia, and lobular or ductal carcinoma in situ.
<br />
<br /> - The identification of cytological or histological abnormalities in breast epithelial
<br /> cells is an important component of risk assessment.
<br />
<br /> Objective:
<br />
<br /> Primary objectives are:
<br />
<br /> - To determine the incidence and nature of cytologic changes in ductal epithelial cells
<br /> from the high-risk breast, in specimens collected by breast ductal lavage, and to
<br /> determine if these cytologic findings are different from those of female normal
<br /> volunteers not at increased risk for breast cancer.
<br />
<br /> - To characterize by breast duct endoscopy, high risk breast ductal epithelium and
<br /> architecture, and correlate these findings with the cytologic findings referenced in
<br /> above bullet.
<br />
<br /> - To determine what is the global gene expression pattern of high risk breast epithelial
<br /> cells from the high risk breast, and does this differ from that of breast epithelial
<br /> cells from female normal volunteersnot at increased risk for breast cancer. The gene
<br /> expression profile will be determined by cDNA microarray and validated by RT-PCR.
<br />
<br /> Eligibility:
<br />
<br /> Eligibility for high risk individuals will include:
<br />
<br /> - Women with a unilateral invasive or noninvasive (DCIS) breast cancer of epithelial
<br /> origin.
<br />
<br /> - Women without breast cancer, but with a Gail Index greater than 1.67 percent, or a
<br /> cumulative lifetime risk greater than or equal to double the age- and race-matched
<br /> general population risk.
<br />
<br /> - Women known to be BRCA1/2 or other hereditary genes mutation carriers.
<br />
<br /> - Women with cytologic or histologic evidence of ductal hyperplasia, atypical ductal
<br /> hyperplasia, or lobular carcinoma in situ.
<br />
<br /> - Women may be either premenopausal or postmenopausal. Postmenopausal is defined by the
<br /> absence of menstrual periods for at least 12 months.
<br />
<br /> - Postmenopausal women who have previously undergone a hysterectomy without oophorectomy
<br /> must have a serum FSH level of > 40 IU/ml, and a serum estradiol level of less than40
<br /> pg/ml to document postmenopausal status.
<br />
<br /> Eligibility for normal volunteers will include:
<br />
<br /> - Women who are premenopausal or postmenopausal with a Gail model risk index less than
<br /> 1.67 percent, and without a cumulative lifetime risk greater than or equal to double the
<br /> age- and racematched general population risk.
<br />
<br /> - Women who have previously undergone a hysterectomy without oophorectomy must have a
<br /> serum FSH level of >40 IU/ml, and a serum estradiol level of less than 40 pg/ml to
<br /> document postmenopausal status.
<br />
<br /> - Both breasts must be free of any suspicious areas by physical examination and, for women
<br /> over 30 years of age by mammogram. There must be no history of atypical hyperplasia,
<br /> invasive or in situ carcinoma.
<br />
<br /> Both groups must have acceptable white blood cell and platelet counts.
<br />
<br /> Design:
<br />
<br /> Breast ductal epithelial cells will be collected by breast ductal lavage from (a) the breast
<br /> in women at increased risk for breast cancer, and (b) the breast of female normal volunteers
<br /> who are not at increased risk for breast cancer.
<br />
<br /> Ductal epithelial cell specimens will be analyzed cytologically for the presence of
<br /> hyperplasia, atypia, or in situ changes.
<br />
<br /> Breast duct endoscopy will be performed in breast cancer patients and in normal volunteers
<br /> with cytologic atypia on ductal lavage to determine ductal architectural changes associated
<br /> with increased risk for breast cancer, and to provide correlation with cytologic atypia.
<br />
<br /> The gene expression profile of normal and high-risk ductal epithelial cells will be studied
<br /> by cDNA-microarray to determine changes in gene expression associated with increased risk for
<br /> breast cancer.
<br />
<br /> Additional molecular profiling experiments which will be performed as lavage cells are
<br /> available include DNA whole exome sequencing, Comparative Genomic Hybridization (CGH),
<br /> proteomic tissue lysate arrays, and identification of mammary stem cells.
<br />
<br /> A total of 104 high-risk subjects and 110 normal volunteers will be studied, divided
<br /> 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:
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 > 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 < 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 < 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 > 40 IU/mL, and a serum estradiol level of < 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.
Outcome Measures
Outcome measures are the tests that investigators perform to prove whether or not a treatment being tested in a clinical trial is having any effect.
Primary
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.
Primary
Characterize high-risk breast ductal epithelium and architecture.
Characterize by breast duct endoscopy, and correlate these findings with the cytologic findings.
Primary
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.
Secondary
Examine ductal epithelial cell preparations for the presence of mammary stem cells.
From both women at high risk and from women not at high risk for breast cancer.
Secondary
Determine the pattern of protein expression for selected proteins in the high-risk epithelial cells.
Using proteomics tissue lysate arrays.
Secondary
Determine the gross genomic alterations present in high-risk breast epithelial cells.
Using comparative genomic hybridization.
Secondary
Determine the DNA mutational pattern of breast epithelium from women at high risk for breast cancer.
Using DNA whole exome sequencing.
Study 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