Discovery of protein fragment that helps predict breast cancer outcome

Oregon Health & Science University Cancer Institute researchers have identified a protein fragment in some human breast cancers that may help predict a patient's chances of survival.

The presence of the fragment, called p95HER-2, in breast cancer tissue correlates closely with lymph node metastasis and earlier recurrence of the disease, suggesting that p95HER-2 is a marker and perhaps even involved in metastasis.

"By studying this marker we have a better chance to identify the patients who are more likely to have a longer disease-free survival," said Edward Keenan, Ph.D., one of the authors of the study. Keenan is professor of physiology and pharmacology and associate dean for medical education, OHSU School of Medicine.

The study, conducted in the lab of Gail Clinton, Ph.D., professor of biochemistry and molecular biology, OHSU School of Medicine, in collaboration with Keenan and investigators in Spain led by Jose Baselga, M.D., will be published on Jan. 15 in Clinical Cancer Research, a journal published by the American Association for Cancer Research.

The study builds on observations the investigators have published over the last five years about the role of the HER-2 oncogene in breast cancer. HER-2, a growth factor receptor, is overexpressed in 20 to 30 percent of breast cancer cases, but it has had limited usefulness in predicting clinical outcomes, particularly in early-stage breast cancer.

Clinton's lab identified a fragment of full-length p185HER-2 that results from HER-2 cleavage, called p95HER-2, and developed an antibody that recognized it, making it possible to study the role of p95HER-2 in the spread of breast cancer.

The researchers studied breast cancer tissue from 483 biopsies from hospitals in the United States and Spain representing all stages of the disease. Two forms of the HER-2 protein were investigated: the full-length p185HER-2 receptor and its truncated form, p95HER-2. Only the truncated form proved to be a significant independent prognostic factor regarding clinical outcomes.

"More work is needed to determine if the presence of p95 has any significance regarding responsiveness of the cancers to chemotherapy, anti-estrogen therapy or Herceptin [a drug therapy for HER-2-related metastatic breast cancer]," Keenan said. "Hopefully, understanding the significance of this marker will help us better specify effective therapy for individual patients."

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