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 Penn vet research identifies new target for taming Ebola
12.01.2017 | University of Pennsylvania

nachricht The strange double life of Dab2
10.01.2017 | University of Miami Miller School of Medicine

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: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

Im Focus: How to inflate a hardened concrete shell with a weight of 80 t

At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).

Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...

Im Focus: Bacterial Pac Man molecule snaps at sugar

Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.

The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

Nothing will happen without batteries making it happen!

05.01.2017 | Event News

 
Latest News

Water - as the underlying driver of the Earth’s carbon cycle

17.01.2017 | Earth Sciences

Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

17.01.2017 | Materials Sciences

Smart homes will “LISTEN” to your voice

17.01.2017 | Architecture and Construction

VideoLinks
B2B-VideoLinks
More VideoLinks >>>