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Gene Predicts Breast Cancer Prognosis
Date:4/23/2008

Experiments in mice could lead to better diagnosis and treatment, experts say

WEDNESDAY, April 23 (HealthDay News) -- A protein that stops the spread of breast cancer tumors in mice can predict which malignancies might spread, a new study suggests.

The gene, called bromodomain protein (Brd4), when added to breast cancer cells in mice, produced a unique gene signature, which was also detected in human breast cancer patients.

"We have identified that this particular gene seems to be associated with outcomes in breast cancer," said lead researcher Kent W. Hunter, a senior investigator at the U.S. National Cancer Institute. "This gene may be something we want to investigate in more detail."

Understanding how the new gene functions may lead to a better understanding of what makes breast cancer metastasize, Hunter said. "This will help identify patients who will have a better or worse outcome," he added.

The report was published in this week's issue of the Proceedings of the National Academy of Sciences.

In the study, Hunter's team inserted the gene for the Brd4 proteins into mouse breast cancer tumor cells that are known for their ability to metastasize.

However, tumor cells that contained Brd4 produced smaller tumors that did not metastasize as readily. In addition, Brd4 changed many other genes, resulting in a unique genetic signature.

The researchers then mapped the signature genes to corresponding human genes, and compared the human Brd4 signature with patient data from five large groups of breast cancer patients.

In all five groups, those patients who had the Brd4-positive signature lived longer and had a lower incidence of metastatic tumors, the researchers found. This indicates that the Brd4 gene expression signatures could accurately predict the severity of breast cancer, the researchers said.

These findings may lead to new treatments, Hunter said.

"We may not only be able to find a prognostic signature, but we can identify other genetic elements that are driving prognosis, so we may also be able to develop additional therapeutic strategies," Hunter said. "We may be able to find new drugs or strategies to improve quality of life and extend life span."

One expert doesn't think this gene makes a contribution to predicting the prognosis of breast cancer.

"This is a marker study looking at a novel gene and its expression, and suggests that the gene expression may predict outcome in node-negative, estrogen-positive breast cancer," said Dr. Harold J. Burstein, an assistant professor of medicine at Dana-Farber Cancer Institute, Brigham and Women's Hospital and Harvard Medical School.

"There are already multiple, commercially available gene expression array tests such as Oncotype DX, MammaPrint, with more extensive clinical support for similar patients," Burstein said. "Most investigators believe that multiple gene assays are more informative than single gene assays."

"Finally, the clinical validation in this experience is drawn from small sets of patients, and the strength of the data suggest modest, if any, real contribution for this gene," Burstein said.

More information

For more on breast cancer, visit the U.S. National Cancer Institute.



SOURCES: Kent W. Hunter, Ph.D., senior investigator, U.S. National Cancer Institute, Bethesda, Md.; Harold J. Burstein, M.D., Ph.D., assistant professor, medicine, Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School, Boston; April 21-25, 2008, Proceedings of the National Academy of Sciences


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