Researchers find connection between protein, prognosis in breast cancer

Oregon Health & Science University Cancer Institute researchers have found that a tumor protein present in an aggressive form of breast cancer is related to a poor prognosis.

The presence of the protein, called growth factor receptor-bound protein-7, often referred to as GRB-7, in breast cancer tumors, is strongly related to the growth and spread of the cancer, according to principal investigator Shiuh-Wen Luoh, M.D., Ph.D., assistant professor of medicine (hematology/medical oncology) in the OHSU School of Medicine.

The research will be presented Sunday, April 13, at 1 p.m. at the annual American Association for Cancer Research meeting in San Diego.

The GRB-7 protein previously has been shown to be important to cell communication in the spread of cancer. The GRB-7 gene is located close to the HER-2/Neu gene that regulates breast cancer growth. The OHSU Cancer Institute researchers discovered that the levels of GRB-7 protein are often heightened at the same time that HER-2/Neu levels are high. Also, not infrequently, they found breast tumors that overexpressed one but not the other protein. Overexpression means that there is an abundant presence of the protein.

“It is surprising that we found discordance in the overexpression of these genes because they are so close together,” Luoh said.

Researchers analyzed 563 primary breast cancer specimens. The samples were collected during a 20 year period for the OHSU Cancer Institute Breast Tumor and Clinical Data Repository.

The OHSU study shows that one in six breast tumors have high GRB-7 protein. These tumors have more aggressive, fast-growing and fast-spreading characteristics. HER-2/Neu positive tumors do not show these same features.

“We think that identifying the individual contribution of the GRB-7 and its interaction with HER-2/ Neu gene may eventually help physicians better predict the clinical course of breast cancer in their patients. Also, new treatments might be designed to interfere with the actions of GRB-7 that can stop the growth and spread of a portion of breast cancer tumors,” Luoh said.

Researchers have known that not all HER-2/Neu positive breast cancers shrink or slow their growth when treated with Trastuzumab or Lapatinib, targeted therapies against HER-2/Neu. The researchers speculate that GRB-7 might influence a tumor’s response to treatment. These findings are preliminary but could eventually lead to a clinical test for GRB-7 and better treatment for patients with GRB-7 positive breast tumors, Luoh explained.

The study was funded by the OHSU Cancer Institute, the OHSU Division of Hematology and Oncology, and the Portland Veterans Affairs Research Foundation.

Other researchers include: Tao Bai; Betsy Ramsey, both research associates and Edward Keenan, Ph.D., associate dean for medical education and professor of pharmacology and physiology, and surgery, OHSU School of Medicine. Luoh is also a member of the OHSU Cancer Institute’s Comprehensive Breast Cancer Clinic, which focuses on a multidisciplinary approach to cancer care and he is also affiliated with the Portland Veterans Affairs Medical Center.

The OHSU Cancer Institute is the only National Cancer Institute-designated center between Sacramento and Seattle. It comprises some 200 clinical researchers, basic scientists and population scientists who work together to translate scientific discoveries into longer and better lives for Oregon's cancer patients. In the lab, basic scientists examine cancer cells and normal cells to uncover molecular abnormalities that cause the disease. This basic science informs more than 300 clinical trials conducted at the OHSU Cancer Institute.

Oregon Health & Science University Cancer Institute Director Brian J. Druker, M.D., will be giving one of the plenary sessions at this year’s American Association for Cancer Research annual meeting on Sunday, April 13 in San Diego, Calif., titled “Accelerating the pace of cancer drug development: Target identification and clinical trials.”

Visit http://www.aacr.org/home/scientists/meetings–workshops/annual-meeting-2008.aspx for more information.