Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New Breast Pap Smear Detects Early Cellular Changes; May Prevent Onset of Breast Cancer

05.03.2004


Long before a woman feels an ominous lump in her breast, Victoria Seewaldt, M.D., can test her for subtle signs that breast cancer may be brewing in a few errant cells amidst thousands of healthy ones. Never before has such a possibility existed, and Seewaldt is brimming with excitement.


Victoria L. Seewaldt, M.D.
PHOTO CREDIT: Duke University Medical Center



"This is potentially the ’breast pap smear’ that we never had before," said Seewaldt, a scientist and breast oncologist at the Duke Comprehensive Cancer Center. "Just as we do with a cervical pap smear, we can now survey cells from the whole breast, examine them under the microscope and test for early changes that often precede breast cancer. Then we can give women a preventive agent to see if we can eradicate her abnormal cells and thus prevent cancer from developing."

The new test, developed at University of Kansas Medical Center and refined at the Duke Comprehensive Cancer Center, will be undergoing clinical trials at three centers nationwide. It is far more sensitive than a mammogram because a pathologist analyzes each cell for specific molecular changes that are common to many breast cancers, said Seewaldt, director of Duke’s new Breast Health Clinic. It is especially useful for detecting changes in dense breasts, which are typically quite difficult to image using mammography.


In the test, physicians use a slender needle to extract cells from segments of the entire breast. Doctors then test each breast cell for specific genetic changes, as well as for abnormally shaped cells that are deemed "atypical."

Carol Fabian, M.D., at the University of Kansas Medical Center, has shown that even a smattering of atypical cells confers a four-fold increase in a woman’s risk of breast cancer. And many scientists have linked specific gene alterations with the development of breast cancer. But further than that, scientists are unclear as to how breast cancers arise.

The new "breast pap smear" will help characterize a cell as it transforms from normal to abnormal, and then eventually into a malignant cell, said Seewaldt. Understanding how cells behave very early in the process of becoming cancerous can help doctors assess a woman’s potential cancer risk -- and hopefully even prevent cancer -- long before cellular changes have become irreversible, she said.

"Ninety percent of breast cancers occur randomly, without a family history of the disease or a known genetic mutation in the woman, said Seewaldt. "Clearly, we don’t understand how most breast cancers arise, and we don’t know how the various agents we give to patients actually repair what is malfunctioning.

"The new test will define what early changes in the breast looks like, and furthermore, it will tell a woman early on if a preventive treatment is really working in her own body."

In particular, the test will detect the presence or absence of a specific gene called RAR beta. This gene regulates how breast cells use vitamin A in order to maintain their proper health. Studies have shown that RAR beta loses its ability to function in many women with breast cancer.

If RAR beta is present inside cells, vitamin A can do its job: regulating how breast epithelial cells grow, divide and eventually die at the appropriate time. Without RAR beta, vitamin A doesn’t work and breast epithelial cells embark on the road toward cancer. Hence, RAR beta is a good molecular "marker" by which to assess the potential risk of developing breast cancer.

Even a few breast epithelial cells that show loss of RAR beta function could signal an increased risk for breast cancer, said Seewaldt. A few abnormal cells likely reside in a field of many abnormal cells. Thus, a woman who shows even a sprinkling of cells without RAR beta will be given a preventive agent such as beta-carotene, flax seed oil, tamoxifen or a COX 2 inhibitor to determine if one of these agents can eradicate the abnormal cells.

"RAR beta gives us a potential marker to monitor if the preventive agents we’re giving have an impact on preventing breast cancer," said Seewaldt. "We’ll test the women before, during and after treatment to see if any of the various agents are able to reduce the number of abnormal cells."

Women aged 35 to 55 who are at high risk for breast cancer are eligible to join the clinical trial. High risk is defined as having two first degree relatives who had breast cancer; an abnormal breast biopsy or mammogram or a carrier of BRCA 1 or 2 -- genes that confer a 90 percent lifetime risk of breast cancer.

Despite these criteria, Seewaldt cautions that there is no definitive way to measure risk without a test because the majority of breast cancers develop at random.

"As women in America, we are all at risk for breast cancer," said Seewaldt. "Mammograms and self breast exams are good tests for looking at cancer, but they don’t always do a good job of finding early changes in the breast."

While the test is only available at three clinical sites (Duke, Kansas and Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at The Ohio State University) as part of a clinical trial, Seewaldt hopes it will ultimately be available at numerous sites around the country. The test is cheap and so simple to administer and analyze that even a basic clinical laboratory could carry it out, she added. It requires only a syringe and pap smear fluid -- no refrigeration or special preservation -- and a simple "PCR" test to amplify genes that even a high school student could perform in the laboratory.

The test works as follows: the breast is first numbed with a local anesthetic, a slender needle is inserted into the inner quadrant of the breast, then it is slightly withdrawn and reinserted eight to 10 times in precisely defined segments of the breast. The process, called random fine needle aspiration, is repeated on the breast’s outer quadrant to ensure that cells are extracted from the entire breast.

The samples of breast tissue are analyzed for signs of atypia, including a critical alteration to RAR beta in which the gene is silenced by methylation. Methylation is thought to be triggered by environmental factors such as diet, nutrition, smoking and chemical exposures. These environmental triggers prompt a group of molecules to attach to a gene and convey a message to silence or reduce its expression. The gene itself remains unchanged, which is why scientists can’t search for a mutation in the gene.

Seewaldt describes methylation as like putting gum on a light switch. The light isn’t broken, but it can’t be switched on.

When RAR beta isn’t turned on, it can’t signal two other important tumor suppressor genes -- CBP and p300 -- which are also critical in regulating how a cell grows.

One key to reversing the methylation of RAR beta could lie in vitamin A and substances similar to vitamin A, said Seewaldt. Her recent studies have shown that vitamin A can actually demethylate RAR beta. In doing so, vitamin A initiates an important feedback loop that suppresses tumor growth in this way:
  • Vitamin A turns on the RAR beta gene
  • The RAR beta gene expresses a protein called a receptor
  • The receptor acts like a dock that receives messages from hormones, vitamins, and the environment and conveys them inside the cell
  • the messages are transmitted to CBP and p300
  • CBP and p300 express their own proteins that enable the cell to better utilize vitamin A for its tumor-suppressing activities.

Seewaldt likens the process to a relay race. If one first runner doesn’t connect with the next runner, the entire loop is broken.

"We’ve always known that vitamins are important in the prevention of cancer, but here is a clear-cut example at the cellular level demonstrating that normal amounts of fresh vegetables -- leafy greens, carrots, sweet potatoes -- may be very important in preventing breast cancer."

Seewaldt said the ultimate goal of the clinical trial and its associated research is to identify which cellular changes progress to become cancer, and which cellular changes are benign.

"What cellular changes promote the growth of breast cancer, and which agents can halt that progression? These are the questions we hope to answer."

Becky Levine | dukemed news
Further information:
http://dukemednews.org/news/article.php?id=7450

More articles from Health and Medicine:

nachricht Study suggests possible new target for treating and preventing Alzheimer's
02.12.2016 | Oregon Health & Science University

nachricht The first analysis of Ewing's sarcoma methyloma opens doors to new treatments
01.12.2016 | IDIBELL-Bellvitge Biomedical Research Institute

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

NASA's AIM observes early noctilucent ice clouds over Antarctica

05.12.2016 | Earth Sciences

Shape matters when light meets atom

05.12.2016 | Physics and Astronomy

Researchers uncover protein-based “cancer signature”

05.12.2016 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>