Breast 'Pap Smear' Predicts Likely Cancer

New Test May Prevent Onset of Cancer by Identifying Early Cell Changes

From the WebMD Archives

March 5, 2004 -- A new test is being evaluated that could predict the likely development of breast cancer in high-risk women -- allowing for treatment years before the disease is diagnosed on screening tools such as mammogram or MRI.

The test -- dubbed a "breast Pap smear" -- entails extracting cells from breast tissue with a needle and examining them for changes that typically lead to full-blown cancer.

If it proves fruitful in clinical trials just getting started, the test could prove to be a major breakthrough, both for women at higher risk for breast cancer and the researchers who study and treat them.

"What we do is examine these harvested cells to see if they are atypical -- that is, they are not normal but not yet cancerous," says Carol Fabian, MD, of the University of Kansas Medical Center, who developed the test. "What we have discovered in past research is that women with these atypical cells face a fivefold increase of developing either invasive or noninvasive breast cancer within four years."


That discovery, detailed in a study she published four years ago in the Journal of the National Cancer Institute, led to new clinical trials just getting started at her breast cancer center, as well as at Duke University and Ohio State. About 200 women, all deemed to be at high-risk for breast cancer because they have mutations in the so-called BRCA "breast cancer genes" or a strong family history of the disease, are being recruited for these trials.

"This very simple, relatively painless test could tremendously refine our short-term risk predictions," Fabian tells WebMD. "It's screening cells to detect changes in them that predict the likely development of breast cancer before there is actual cancer."

While it would be several years before the test reaches the market -- assuming the new clinical trials prove it to be effective -- some experts say the test offers great potential.

"It's still too early to say that this is a major breakthrough, but the potential is enormous," says National Cancer Institute investigator Victor G. Vogel, MD, MHS, who directs the University of Pittsburgh's Magee-Womens Breast Cancer Program. He is not involved in the trials or the test itself.

"The whole notion of being able to get cells from the breast and look at their biological profile, rather than just a woman's breast cancer risk profile, can potentially be a major development," he tells WebMD.

How It Works

The test involves harvesting cells at eight specific sites in the breast and then having each cell individually evaluated by a specially trained pathologist to determine which ones are abnormally shaped, indicating they are "atypical" and likely to be precancerous.

"This would not replace mammograms, but [would] be another tool to monitor high-risk women," says Victoria Seewaldt, MD, director of Duke's Comprehensive Cancer Center, who is involved in the trials. "The advantage it offers is that unlike mammogram or MRI, which detect cancer that has already developed, this test allows us to survey individual cells from breast tissue and examine them under a microscope for early changes that often precede breast cancer, just as a Pap smear predicts cervical cancer."

Not only would this allow for early treatment with "pre-cancer" drugs to stop cancer before it fully develops, but it would allow scientists to better track which of these treatments are most effective at eradicating these abnormal cells. Agents being explored with this test as part of the new trials include Cox-2 inhibitors such as Celebrex, beta-carotene, flaxseed oil, and the breast cancer drug tamoxifen.


"We could administer chemo-preventative therapy to high-risk women and then sample their breast tissue cells six or 12 months later to see what is working and what isn't," Seewaldt tells WebMD. "It could be huge, because currently when we do clinical trials, we look at the end point -- whether there is cancer or no cancer -- and we sometimes have to guess on how we got there."

The test is not designed to screen all women, like mammogram or MRI, but rather only those with a strong family history of breast cancer, mutations in BRCA1 and BRCA2 genes, a history of abnormal breast biopsies, or with dense breast tissue that make mammograms hard to read. It would also be used to track women who have already been treated for breast cancer to further track their remission, says Seewaldt.

"Many women, especially those with super dense breast tissue, can do all the right things such as get regular mammograms and cancer still seems to come out of nowhere," she tells WebMD. "But since cancer takes 10 to 20 years to develop, this would allow high-risk women to get an early jump on treatment before breast cancer actually fully develops."


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SOURCES: Carol Fabian, MD, director, Breast Cancer Prevention Center; professor of medicine, University of Kansas Medical Center, Kansas City, Kan. Victor G. Vogel, MD, MHS, professor of medicine and epidemiology; director, Magee-Womens Breast Cancer Program, University of Pittsburgh School of Medicine; investigator, the National Cancer Institute, Bethesda, Md. Victoria Seewaldt, MD, associate professor of medical oncology; director, Breast Cancer Prevention Program, Duke University Comprehensive Cancer Center, Durham, N.C. Fabian, C. Journal of the National Cancer Institute, Aug. 2, 2000; vol 92: pp 1217-1227.
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