"Pap Test” to Detect Changes Preceding Breast Cancer

In a new procedure, cells are extracted from segments of the entire breast and analyzed to see if genetic changes have occurred or if abnormally shaped cells are deemed atypical, in order to assess a woman's potential cancer risk.

In particular, the test will tell if a specific gene called RAR beta is present. This gene regulates the way breast cells use vitamin A in order to maintain proper health. Studies have found that RAR beta loses its ability to function in many women with breast cancer. If RAR beta is inside cells, vitamin A can do its job of regulating how breast epithelial cells grow, divide, and eventually die. Without RAR beta, vitamin A does not work, and breast epithelial cells embark on the road to cancer. Therefore, RAR beta is a good molecular marker for assessing the risk of breast cancer.

The new test was developed at the University of Kansas Medical Center (Kansas City, KS, USA; www.kumc.edu) and refined at the Duke Comprehensive Cancer Center (Durham, NC, USA; www.cancer.duke.edu). The researchers say the test is far more sensitive than a mammogram because a pathologist analyzes each cell for specific molecular changes common to many breast cancers. Also, the test is especially useful for detecting changes in dense breasts, which are difficult to image with mammography.

"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,” said Dr. Victoria Seewaldt, a scientist and breast oncologist at Duke Comprehensive Cancer Center.

In a process called random fine needle aspiration, the breast is first numbed with a local anesthetic and a slender needle is inserted into the inner quadrant of the breast, then is slightly withdrawn and reinserted eight to 10 times in precisely defined segments of the breast. The process is repeated on the breast's outer quadrant to ensure that cells have been extracted from the entire breast.

All the samples of tissue are analyzed for atypical signs, including an important alteration to RAR beta in which the gene is silenced by methylation. Scientists think methylation is triggered by such environmental factors as diet, nutrition, smoking, and exposure to certain chemicals. These triggers prompt a group of molecules to attach to a gene and convey a message to silence or reduce its expression. However, the gene itself remains unchanged, so scientists cannot search for a mutation. Dr. Seewaldt has found that vitamin A can actually demethylate RAR beta, initiating an important feedback loop that suppresses tumor growth.

"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,” said Dr. Seewaldt.

Currently, the test is undergoing clinical trials at three U.S. centers. The test is cheap and easy to administer and analyze, requiring only a syringe, pap smear fluid, and a simple polymerase chain reaction (PCR) test. According to Dr. Seewaldt, "The new test will define what early changes in the breast look like, and furthermore, it will tell a woman early on if a preventive treatment is really working in her own body.”




Related Links:
U. of Kansas
Duke Cancer Center