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    Posted: 05/30/2002
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BenchMarks
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    Volume 7, Issue 4

Private-Public Partnerships in Cancer Vaccine Research

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Report to Nation Finds Declines in Cancer Incidence, Death Rates

High Dose Chemotherapy Prolongs Survival for Leukemia

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Past Highlights
Collecting Cells for Breast Cancer Biomarker Research - Nipple Aspiration and Ductal Lavage

The vast majority of breast cancers originate in cells that line the inside of the milk ducts in the breast. Changes in these cells, which are known as mammary epithelial cells, have been associated with an increased risk of breast cancer in some studies. Researchers hope that by identifying specific changes that occur in these cells during the initial stages of breast cancer, they may be able to detect the disease earlier and develop new approaches to cancer prevention.

The National Cancer Institute (NCI) is supporting research to identify differences between normal breast epithelial cells and those that are likely to develop into cancer. Nipple aspiration, ductal lavage, fine needle aspiration, and breast biopsy are methods commonly used to collect the cells used in these studies.

1. How can the examination of breast fluids improve breast cancer detection?

The NCI is funding several studies to help determine when cells lining the milk duct have begun to develop into cancer. Scientists are investigating whether specific proteins, patterns of proteins, or changes in DNA in these fluids may be useful as early indicators of cancer. Some researchers are also investigating whether the presence of atypical cells in breast fluid corresponds to an increased risk of cancer.

2. What is nipple aspiration?

Nipple aspiration uses gentle suction to collect fluid from the nipple. This is done with a device similar to the breast pumps used by nursing women. Fluid containing cells from the lining of the ducts can be obtained from about 75 percent of women in this manner. Typically, only a tiny amount of fluid and a few cells can be obtained; the quantity and quality of the fluid collected limits the types of studies than can be done.

3. What is ductal lavage?

Ductal lavage is a new technique to collect cells from the lining of the milk duct. In this procedure, nipple aspiration is first used to draw a tiny amount of fluid to the surface of the nipple to locate the milk ducts. A slender catheter is then inserted into the duct through the natural opening. A small amount of anesthetic is infused into the duct through the catheter, followed by a small amount of saline. This saline rinses through the duct, collecting cells, and is then withdrawn. This minimally invasive procedure produces many more cells than the other methods commonly used to collect cells from the milk ducts.

4. What other techniques can be used to collect cells from the milk ducts?

Researchers sometimes use fine needle aspiration or needle biopsy (procedures commonly used to diagnose abnormal breast growth) to collect milk duct cells for study.

Infine needle aspiration, researchers insert a thin needle into the breast tissue and apply mild pressure to withdraw cells and fluid directly. This procedure can be used to obtain fluid from almost all women. However, the quantity of material obtained is limited.

A needle biopsy is obtained by inserting a larger, hollow needle into the breast to obtain a slender sample of breast tissue. This procedure is more invasive than the other techniques described here and may cause changes in subsequent mammograms. Because most of the breast is composed of supporting tissue, only a small percentage of a biopsy sample contains cells from the milk ducts.

5. Are these techniques currently being used by physicians to assess breast cancer risk?

Today, these techniques are primarily research tools for obtaining epithelial cells. There is no protein or DNA biomarker from nipple aspirate fluid that is currently used in standard practice that will predict whether someone is likely to develop breast cancer.

Some physicians are collecting cells by nipple aspiration, ductal lavage, and fine needle aspiration. A pathologist then examines the samples under a microscope for atypical cells to help assess the risk of breast cancer. However, there is insufficient scientific evidence to support this procedure. Long-term studies have not been done to determine whether screening for atypical cells decreases breast cancer mortality.

The presence of atypical cells from nipple or fine needle aspiration has been linked to an increased risk of cancer within the three to five years following testing, and it is generally assumed that atypical cells obtained using ductal lavage would indicate a similar risk. However, because fluid is not usually collected from all of the milk ducts during these procedures, it is unclear what conclusions can be drawn if no atypical cells are present in a sample.

6. How might nipple aspiration or ductal lavage be used in practice someday?

If further research validates nipple aspiration or ductal lavage for breast cancer risk assessment, either by biomarkers analysis or atypical cells, the results of such tests would be considered in conjunction with other risk factors, such as age and family history. Women and their physicians could then use the information to make decisions about breast cancer prevention and screening.

7. Will these techniques replace mammography for breast cancer screening?

If researchers are able to identify useful biomarkers for breast cancer, ductal lavage ornipple aspiration will likely be used in combination with mammography to provide a more complete assessment of breast health.

8. What are some of the NCI-funded studies currently investigating nipple aspirate fluid for the early detection of breast cancer?

These studies include:

• Pilot Screening Study of Breast Imaging Outcome Measures in Women at High Genetic Risk of Breast Cancer

This clinical trial is assessing ductal lavage as a method to obtain cell samples from high-risk premenopausal women for evaluation and biomarker studies. This trial is not currently recruiting, but may do so in the future.

For more information:
http://www.cancer.gov/ClinicalTrials/

• Association of Nipple Aspirates With Clinical Findings

This study is searching for protein biomarkers in nipple aspirate fluid that may be used to detect breast cancer at an early stage.

For more information:
http://researchportfolio.cancer.gov/cgi-bin/abstract.pl?ProjectID=34089

• Cytogenetic Screening of Mammary Epithelial Cells

This study is investigating whether physical changes in the DNA of cells found in nipple aspirate fluid can be used to detect breast cancer at an early stage.

For more information:
http://researchportfolio.cancer.gov/cgi-bin/abstract.pl?ProjectID=34592

• Detecting Breast Cancer Protein Signatures in Body Fluid

This study is investigating whether protein patterns in breast tumor tissue are also detectable in body fluids, including blood serum and nipple aspirate fluid, at an early stage in the development of cancer.

For more information:
http://researchportfolio.cancer.gov/cgi-bin/abstract.pl?ProjectID=20902

• Breast Cancer Diagnosis With BFGF

Basic fibroblast growth factor is a protein that is present at an abnormally high level in the nipple aspirate fluid of breast cancer patients. This study is investigating whether the level of this protein is also elevated during early stages of the disease and may be useful for early detection.

For more information:
http://researchportfolio.cancer.gov/cgi-bin/abstract.pl?ProjectID=33181

• Chemoprevention for Women at High Risk of Breast Cancer

This study is investigating whether the chemoprevention drug difluoromethylomithine can reverse the presence of atypical cells in nipple aspirate fluid.

For more information:
http://researchportfolio.cancer.gov/cgi-bin/abstract.pl?ProjectID=36023

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