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Herceptin effective in breast cancer cells with low HER-2 levels

Chicago -- Northwestern University and Evanston Northwestern Healthcare researchers have discovered that the monoclonal antibody Herceptin (trastuzumab) used in combination with certain cancer chemotherapies effectively treats breast cancer tumors that produce low or undetectable amounts of the HER-2 oncogene but overexpress the growth factor heregulin (HRG), an activator of the HER-2 cancer oncoprotein. Increased levels of HER-2 are associated with poor patient prognosis, enhanced metastasis (cancer spread) and resistance to chemotherapy.

Until now it was believed that trastuzumab combined with cytotoxic drug therapy was effective only in HER-2--positive, or HER-2--overexpressing, breast cancer which represents about 25 percent of all breast cancers, said Dr. Ruth Lupu, director of translational breast cancer research at the Evanston Northwestern Healthcare Research Institute, who led the study, published in the August 10 issue of the Journal of Clinical Oncology.

Lupu is also professor of medicine at Northwestern University Feinberg School of Medicine and a researcher at The Robert H. Lurie Comprehensive Cancer Center of Northwestern University.

The study was conducted as part of the Cancer Center's breast cancer SPORE (Specialized Program of Research Excellence) grant.

In their study Lupu and colleagues Javier A. Menendez and Inderjit Mehmi of the Evanston Northwestern Healthcare Research Institute found that HER-2 must be activated to exert its malignant effects. HER-2 is capable of being activated by either overexpression (overproduction) or transactivation -- when a protein at one location is activated by the presence of a particular protein at another location.

HRG is an activator of the HER-2 oncogene, promoting breast cancer growth and tumor formation in laboratory models. Dr. Lupu has previously shown that blocking HRG expression inhibits tumor growth and spread of breast cancer cells. HRG is express
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Contact: Elizabeth Crown
e-crown@northwestern.edu
312-503-8928
Northwestern University
10-Aug-2006


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