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Researchers say Friday that overexpression of the molecule known as HER2/neu appears to indicate additional danger to a breast cancer patient if new tests find that the protein is in an active state-and that occurs only in a minority of cases. "Using our new test that measures activation of HER-2/neu we were surprised to find that the majority of tumors actually had the protein in the resting state," said Dr. Michael DiGiovanna, MD, Ph.D., assistant professor of medicine and pharmacology at Yale University School of Medicine, New Haven, Conn. "That would suggests that those were not aggressive tumors. There were only 12 percent of the tumors that had HER-2/neu in the activated state."
HER2/neu is the protein that is the target of Herceptin, a genetically engineered drug developed by Genentech of South San Francisco, Calif. Herceptin has been shown to increase survival among patients with advanced breast cancer. However, Herceptin, when used in conjunction with other anticancer drugs can cause an increased risk of heart muscle damage.
DiGiovanna said his study could help doctors determine who the best candidates for Herceptin would be so that women who would not need or would not be helped by Herceptin could avoid these adverse side effects. DiGiovanna also said the study could help ease the minds of women who fear a diagnosis that their tumor overexpresses HER2/neu-often considered a message that they will have a poor prognosis.
"Most women who have breast cancer and are told they have high levels of HER2/neu would be unhappy to hear that news," said Lynn Matrisian, professor and chairman of cancer biology at Vanderbilt University, Nashville, Tenn. She said patients have come to understand that HER2/neu overexpression means they have a cancer that is likely to recur and spread. But DiGiovanna said his study disputes that current thinking. In his study, DiGiovanna and colleagues examined 816 breast cancers and found that 307 or 38 percent overexpressed HER-2/neu. Of those 37 tumors showed they had activated overexpression - 12 percent of the HER-2/neu tumors; 5 percent of the total cancers studied.
When he looked at outcomes in the 16-year database, DiGiovanna said women with inactive HER-2/neu overexpression had essentially the same features as breast cancer patients without overexpression indicating less aggressive cancers. In contrast, he said, the women with activated HER-2/neu had tumors similar to those cancers associated with aggressive development of the disease.
"Cancer doctors are always looking for better way to predict prognosis," DiGiovanna said, "not only so that we can tell a woman what her prognosis is, but so that we can change the prognosis, so we know how aggressively we have to treat."
Lt. Col. Kenneth Bertram, MD, Ph.D., director of the congressionally directed medical research programs at Fort Detrick, Md., said the work presented by DiGiovanna could help explain why some women respond to Herceptin and others do not. "We may have been provided with another piece of the puzzle," Bertram said, but cautioned that well-designed clinical trials are required to prove DiGiovanna's theory. "We hope in the future," DiGiovanna said, "this may help to guide treatment decisions such as which women need or do not need adjuvant chemotherapy after surgery or how aggressive that chemotherapy has to be. We hope that this test may also have the ability to determine which patients will respond to Herceptin. "But we don't know that yet. Those are studies that we are working on, " he said.
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