Gene Found in 90% of Breast Cancers

Discovery May Lead to Vaccine to Stop the Disease

Researchers hope to use a gene found at high levels in virtually all forms of breast cancer to train the immune system to attack breast cancer cells, a new study reports.

This potential immunotherapy treatment, published in the Aug. 2 issue of the Proceedings of the National Academy of Sciences, would use the gene as a target for a new breast cancer vaccine, says the study's first author Laszlo Radvanyi, Ph.D., associate professor of breast and melanoma medical oncology at M. D. Anderson.

"There are very few bona fide molecular targets that are specific to breast cancer," Radvanyi says. "We wanted highly specific targets for a cancer vaccine, and we believe this is one of them."

Radvanyi was part of a team of scientists at Sanofi Pasteur, Toronto, Canada. Together, they zeroed in on the gene, called TRPS-1, after an exhaustive search for genes found in breast cancer at higher levels than in normal tissue.

Every type of breast cancer contains high levels

Researchers compared the protein levels of more than 50,000 known genes in 54 breast cancer specimens and 289 normal samples.

The type and number of breast cancer specimens included:

• Early breast cancer [ductal carcinoma in situ (DCIS)] (10)
• Locally invasive breast cancers (38)
• Metastatic disease (six)

TRPS-1 was found at high levels in all three forms of breast cancer, but in none of the normal tissue samples, except for low levels commonly found in normal breast tissue.

Gene linked to earliest breast cancer stages

Scientists at other institutions have shown that TRPS-1 is a DNA-binding protein that regulates the production of other proteins needed for the growth and survival of breast cells. It also appears to be involved in recognition of steroids such as estrogen. Radvanyi speculates that the protein, found at high levels in breast cancer, may abnormally regulate cell growth, leading to tumors.

"Based on our findings, we believe that TRPS-1 is involved in the earliest stages of breast cancer," he says.

Gene use similar to treatment with Herceptin

It is hoped that a vaccine activating immune system cells against TRPS-1 will work in a specific way like Herceptin, an antibody that attacks breast cancer cells in which the Her2/neu gene is active. Only about one-third of breast cancer patients are candidates for Herceptin. The vaccine approach studied by Radvanyi does not use antibodies. It attempts to get immune system cells called T-cells to attack the cancer cells.

T-cells are white blood cells that recognize and destroy bacteria, viruses and other foreign matter. Scientists showed that T-cells trained to detect TRPS-1 would attack and kill breast cancer cells containing the TRPS-1 protein.

Treatment would kill cancer, protect normal tissue

"This is exciting because TRPS-1 appears to be abundant only in cancers and not in normal tissue," Radvanyi says. "This makes it much less likely that normal tissue would be attacked."

The next step will be testing more M. D. Anderson patient samples and trying to correlate levels of TRPS-1 to other known breast cancer markers, such as HER2/neu and the estrogen receptor. Researchers also want to understand the protein's targets inside the cell.

"If we understand its targets, in addition to making vaccines against TRPS-1, we might be able to design drugs that disrupt its action, which could be important given the gene's early appearance in breast cancer," Radvanyi says.