A new test that uses milk-duct cells to assess the risk of breast cancer is showing considerable promise and could help more women better understand how likely they are to develop the disease.
Called ductal lavage, the test is designed to detect changes in cells that are the precursors to breast cancer. The minimally invasive test, which can be performed in a doctor's office, is approved for use in high-risk women.
"There's an understandable buzz and interest around it," says Sally Cooper, director of information services for the National Alliance of Breast Cancer Organizations. "The promise of ductal lavage is so immense. But at this point in time, it's for a very specific use."
Enthusiasm is so high, however, that cancer activists--and even the company that makes the technology--say its importance may be exaggerated.
When it was approved for use last year, 1,500 doctors applied to undergo ductal lavage training--considered a large response for a new technology, according to Susan Bro, a spokeswoman for the manufacturer, ProDuct Health, of Menlo Park. So far, doctors have been trained in about 100 centers across the nation
"There has been tremendous demand and inquiry," Bro says.
Ductal lavage, which was developed by breast health expert Dr. Susan Love and researchers at UCLA, is a 20-minute procedure that collects samples of cells from the milk ducts. About 95% of breast cancers are thought to originate in ductal cells.
After many years of growth, these cells form a tumor that can be detected by mammography or during a physical examination. But by that point, the cancer has usually been present for five to 10 years, according to research.
Ductal lavage was designed to find evidence of abnormal or malignant cells before a tumor develops.
If abnormal cells are discovered, a woman can have a biopsy to further examine the tissue, have the duct surgically removed to eliminate the risk, or take tamoxifen, a powerful drug that has been found to reduce the chances of breast cancer in high-risk women.
"I think this is a first big effort in the modern era to address, biologically, the first steps for breast cancer development," says Dr. William C. Dooley, a University of Oklahoma expert who has conducted a major study on ductal lavage. "If women who had invasive breast cancer in one breast have a positive ductal lavage in the opposite breast, then you could benefit from tamoxifen. These women may not otherwise get tamoxifen."
Before the procedure, anesthetic cream is applied to the nipple area. Suction is used to draw tiny amounts of fluid from the milk ducts to the nipple surface. These fluid droplets identify the milk ducts' natural openings.
A hair-thin catheter is inserted into the duct along with anesthetic. A saline solution is then administered to rinse the duct and collect cells. The cells are analyzed for malignancy or for atypia, which means the cells aren't cancerous but aren't normal.
The test, which costs $400 to $800 and may be covered by insurance, can be done in a doctor's office. The majority of the women who have had the test describe it as uncomfortable but not painful, according to ProDuct Health.
"Ducts are distended 600 times their normal size with cells growing in them before you can feel a tumor," Dooley says. "By then, the tumor has usually broken out of the duct and irritated the surrounding tissues. We're looking for that inflammatory response during mammography. But that is five or seven years into the process. So we are really very late with mammography, even though it's our best tool."
However, ductal lavage is not a replacement for mammography or physical breast exam. The Food and Drug Administration approved the technology only for high-risk women and only in conjunction with mammography.
That point may be lost on some enthusiasts of the test, says Barbara Brenner, executive director of Breast Cancer Action, a San Francisco-based consumer advocacy organization. Only one major study has been done on ductal lavage, Brenner points out.
"All of a sudden, everyone is all over ductal lavage saying, 'Oh, look, we've solved the breast cancer detection problem.' We only wish. I think it's fairly clear that it's not quite ready for prime time."
The one study that has propelled ductal lavage into the limelight is an ongoing examination of 507 women at high risk for breast cancer and who had a mammogram or physical exam within 12 months of the start of the study showing no sign of cancer.
High-risk is defined as women who have a personal or family history of breast cancer as well as other factors, such as carrying the BRCA 1 or 2 genes (which significantly increase the risk of breast cancer) or having had two or more benign breast biopsies.
Eighty-four percent of the subjects yielded nipple fluid--a necessary step to allow completion of the procedure. Of these women, 383 underwent the ductal lavage. The laboratory analysis showed that 23.5% of the women had abnormal cells and 0.5% (two women) had malignant cells.
The study was published in April in the Lancet.
"This test is very good at finding risk. This will tell you if you have atypical cells," says Love. "One of the big questions we've had is, when do you take tamoxifen? ... If you are found to have atypia, you could intervene with tamoxifen when it's most helpful."
There are several reasons the test is not considered an early detection test, however, and should not be used for routine screening. Some women (16% in the study) cannot produce nipple fluid--for reasons that aren't clear--that precedes the ductal lavage. And, in 22% (84 women of the 383 study participants), there were not enough cells to adequately analyze the sample.
Even among the women with atypical cells, there is no clear-cut course of action. Women with atypical cells and a family history of breast cancer have a greater chance of developing breast cancer than women who have neither. But atypia may also never result in cancer.
"Are we then going to do surgery on all these women? Are we going to start giving these women very powerful drugs?" Brenner asks. "The question of what to do with this information is something you need to think about very carefully."
According to Cooper, of NABCO, the test may be most helpful to the women who are considering a prophylactic mastectomy but may find--through ductal lavage--that their cells look normal. "Now, maybe you don't have to do a double-mastectomy. You can do ductal lavage. That's a big change," she says.
Studies are also ongoing that may further define the role of the technology, Dooley says.
"The real hope for the future is that out of this can come a variety of tools for monitoring risk and monitoring therapy," he says.
Love, who helped found ProDuct Health and maintains a financial interest in the company, says that ductal lavage has long-term potential as a screening test, much in the same way that Pap smears are used to detect cervical cancer.
A nonprofit foundation in Love's name recently awarded grant money for intraductal research.
"We're trying to get at cancer before it develops," she says. "Perhaps we can find a marker [for cancer] in ductal fluid. It's a big thing now, and I think its potential is enormous."
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Ductal lavage can be performed on women who are at high risk for breast cancer. It helps doctors look for cancer or assess the likelihood that cancer will develop. The process works like this:
A tiny catheter is inserted into the opening of a milk duct. An anesthetic is delivered through the catheter to numb the duct.
Saline is washed into the duct and withdrawn, washing some cells out of the duct.
The collected cells are then sent to a laboratory for analysis.
Source: ProDuct Health Inc.