U.S. Army Medical Research and Materiel Command

September 28, 2002

NOVEL TECHNIQUES FOR PREDICTING RISK OF BREAST CANCER AND FINDING IT EARLY

Points of Contact:
Jennifer Goldberg phone 212/886-2200, email jgoldberg@cwg.com;
Gail Whitehead, Public Affairs Coordinator, phone (301) 619-7783, email gail.whitehead@amedd.army.mil;

Research Results from the "Era of Hope "Department of Defense Breast Cancer Research Program Meeting

ORLANDO, September 28, 2002 - From general screening to specific genotyping, new techniques are making it possible to predict risk of developing cancer, identify its presence, and gauge the odds of relapse after treatment. At the "Era of Hope" Department of Defense Breast Cancer Research Program meeting here, investigators present studies of a sensitive test for trace proteins linked to the disease and a telltale genetic profile for inherited breast cancer.

Test Enables Rapid Screening of Tiny Tissue Samples for Breast Cancer Biomarkers

Researchers have developed a prototype for a simple test that can rapidly screen tiny samples of tissue for "biomarkers" of breast cancer - proteins that signal the presence or recurrence of the disease, according to research presented here.

"This technology allows for the simultaneous testing of many proteins using a very small sample of blood or tissue," said Richard C. Zangar, Ph.D., senior research scientist at the Department of Energy's Pacific Northwest National Laboratory in Richland, WA. The test uses existing technology, which makes it readily transferable to the clinical setting, he added.

Dr. Zangar and his colleagues demonstrated the sensitivity of the test by using it to measure hepatocyte growth factor (HGF), a protein shown to be present at elevated - but still trace - levels in recurrent breast cancer. The test detected levels of HGF that were significantly higher in the blood of breast cancer patients than in control patients. These findings appeared in the May/June issue of Journal of Proteome Research earlier this year.

The technology is expected to be particularly useful for screening proteins in biopsy tissue or in fluid drawn from the nipple, for which samples are small in volume, explained Dr. Zangar. "Old technology" could typically screen for one or two proteins before the valuable sample was used up.

The researchers are now validating the test by using it to screen for multiple proteins simultaneously. They hope that the test may also prove useful at identifying new protein markers that accurately signal the presence or recurrence of breast cancer.

"There are literally hundreds of potential markers," said Dr. Zangar. "And with this technology you can screen hundreds of markers very quickly."

Genotype Plus an Affected Relative Tied to Increased Risk of Breast Cancer

Researchers have identified a genotype associated with breast cancer in recently diagnosed women who claim a first-degree relative (mother and/or sister) with the disease. For women diagnosed at age 50 or before, the link is even stronger.

"Women in the United States whose mother or sister has had breast cancer have twice the risk of developing the disease by age 85 as women in the general population," noted Eldon R. Jupe, Ph.D., Immunobiology and Cancer Program, Oklahoma Medical Research Foundation, Oklahoma City. "But our study now shows that women with both the prohibitin T allele, one of two forms of the prohibitin gene that can occupy the chromosomal slot we investigated, and an affected first-degree relative have an almost five-fold higher risk."

In breast cancer cell lines, Dr. Jupe's previous research has shown that one location on the prohibitin gene is often altered. His research team found that this altered region gives rise to two alleles, referred to as C and T. The C variation codes for an RNA molecule that interferes with the cell cycle and has been shown to suppress tumor growth in animals; the T variation is functionally inactive.

Based on this finding, Dr. Jupe and his team compared prohibitin genotypes in 205 patients and 1,046 control subjects. This study found an increased risk for patients who carried the T allele if a first-degree relative also had breast cancer. An even stronger association, nearly double, was identified in women diagnosed at or before age 50.

"If these findings are validated, they could lead to a greater awareness of the importance of routine breast cancer screening for women with both family and genetic risk factors," Dr. Jupe commented. In the meantime, enrollment in this study continues, with a goal of 400 recently diagnosed women.

The RNA produced from this gene region is a relatively rare molecule - a functional non-coding RNA - meaning that it exerts its influence directly, without having to code for a protein to carry out its function. Although it fits all classic definitions of a tumor suppressor, according to Dr. Jupe, its mechanism of action is unknown. He hopes to elucidate this mechanism and to test other molecular markers potentially connected to breast cancer.

"One day we may be able to use this and other alleles not only to assess risk but possibly to direct treatment," said Dr. Jupe.

"Era of Hope" is a forum for the presentation of research supported by the U.S. Department of Defense's Breast Cancer Research Program (BCRP), an unprecedented partnership between the military, scientists, clinicians, and breast cancer survivors. Since 1992, the BCRP has been working to prevent and cure breast cancer by fostering new directions in research, addressing underserved populations and issues, encouraging the work of new and young scientists and inviting the voice of breast cancer survivors to be heard in all aspects of the program. One of many congressional research programs managed by the U.S. Army Medical Research and Materiel Command, the BCRP has received more than $1.3 billion to date from Congress for innovative breast cancer research.

RC Zangar, RL Woodbury, SM Varnum - General Session: Saturday, September 28, 5:20 p.m.-6:50 p.m., Room 101

"SNP in Prohibitin 3'UTR and Breast Cancer Susceptibility"
E Jupe, M Craft, D Mitchell, L Thompson, J Mulvihill, C Aston - General Session: Saturday, September 28, 5:20 p.m.-6:50 p.m., Room 106