This study will evaluate two potential new methods for detecting breast cancer early: breast duct lavage and breast duct endoscopy. The procedures will be done in women at increased risk of breast cancer and in women at low risk of breast cancer, and the findings will be compared.

Women of any age who have or have had breast cancer in one breast (and are, therefore, at increased risk of cancer in the second breast) and healthy, normal women volunteers at low risk for breast cancer, may be eligible for this study. Candidates are screened with a history and physical examination, blood tests, pregnancy test and mammogram. All participants undergo the following procedures:

Breast Duct Lavage

1. 30 minutes before starting lavage, the participant massages her breast with hand lotion to help increase the number of cells that can be obtained during the procedure.

2. The nipple is then numbed with an anesthetic cream containing lidocaine, a nitroglycerine ointment is applied to the nipple area to help open up the breast ducts, and a warm towel is placed over the breast.

3. Dead skin and body oils are removed from the nipple with a special lotion and the area is then cleaned with alcohol and gauze.

4. A breast pump is placed over the nipple and gentle suction is applied to bring out fluid. If no fluid is obtained, lavage cannot be performed and the procedure will end.

5. If a duct is identified, the participant is given a sedative injected into an arm vein and a very slender tube (catheter) is threaded about 1 inch into the duct. A small amount of lidocaine solution is put through the catheter to numb the inside of the duct. A salt solution is injected into the duct through the catheter. The breast is gently massaged and gentle pressure is applied to draw out fluid.

The procedure is repeated on other milk ducts or to identify a duct. (In general, one or two ducts per breast yield fluid.) The catheter will be in each duct for several minutes. The entire procedure takes 10-30 minutes.

Breast Duct Endoscopy

This procedure is done at the same time as breast duct lavage, also under sedation. The duct that was used for the lavage is used for the endoscopy.

1. A duct at the nipple is gently enlarged with small metal wires, and the ductoscope (a small tube with a camera attached to examine the lining of the duct) is passed into the duct and then further into the breast.

2. Water may be injected through the scope into the duct to open the duct and make it easier to pass the scope.

3. Fluid may be collected through the scope and examined, as was done during lavage.

4. A very thin wire probe may be passed up to several inches into the breast to sample any abnormalities that might be found.

The findings are recorded on videotape. The procedure takes no more than 60 minutes.

Excess material obtained from the procedures may be used for genetic studies and stored for future research. Patients in whom pre-cancerous or cancerous cells are found will be contacted and may have additional studies, such as breast MRI or breast duct x-rays for further evaluation. Patients in whom breast cancer is found will be offered treatment and follow-up (generally for 5 years) at NIH. Women who start taking hormone replacement therapy (HRT) after participating in this study may be asked to repeat the breast duct lavage and possibly breast duct endoscopy after 3 months of HRT to examine the effects of estrogen on breast epithelial cells.

Condition
Breast Neoplasms Healthy

Further Study Details: 

Expected Total Enrollment:  110

The present study will characterize high risk breast ductal epithelium cytologically, by breast duct endoscopy, and by molecular profiling. Breast ductal epithelial cells will be collected by breast duct lavage from a.) the contralateral breast in women with ipsilateral breast cancer, and b.) the breast of female normal volunteers who are not at increased risk for breast cancer. Both premenopausal and postmenopausal women will be studied. 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) and Proteomic tissue lysate arrays. Post menopausal women (normal volunteers) who subsequently receive estrogen replacement therapy will be reexamined three months after initiation of therapy by cytology and cDNA microarray to determine the effects of estrogens on cytology and gene expression of normal breast duct epithelium.

Genders Eligible for Study:  Female

Accepts Healthy Volunteers

Criteria

INCLUSION CRITERIA:
BREAST CANCER PATIENTS:
Women of any age with a unilateral invasive breast cancer of epithelial origin.
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.
Breast cancer may be invasive or noninvasive, and in the past or the present.
The contralateral breast must be free of any suspicious areas by physical examination and mammogram, and without past history of invasive ductal or in situ ductal carcinoma. A past history of atypia or LCIS on a previous biopsy is acceptable.
WBC greater than 2500.
Platelets greater than 50,000.
NORMAL VOLUNTEERS:
Women who are premenopausal or postmenopausal with a Gail model risk index of less than 1.67% are eligible.
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.
Women who plan to initiate hormone replacement therapy (premarin + provera) within the next 3 months and who plan to continue that therapy for at least 3 months will also be eligible.
WBC greater than 2500.
Platelets greater than 50,000.
EXCLUSION CRITERIA:
BREAST CANCER PATIENTS:
Contralateral breast prosthesis.
Pregnancy.
History of radiation therapy to the contralateral breast.
Lactating breast.
Chemotherapy within the past 3 months.
Current antiestrogen therapy.
Current hormonal replacement therapy or oral contraceptives.
Concurrent infection.
Previous contralateral major duct excision.
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.

Maryland
      National Cancer Institute (NCI), 9000 Rockville Pike,  Bethesda,  Maryland,  20892,  United States; Recruiting

Study ID Numbers:  020077; 02-C-0077
Record last reviewed:  November 1, 2004
Last Updated:  March 1, 2005
Record first received:  December 21, 2001
ClinicalTrials.gov Identifier:  NCT00028340
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08