June 6, 2011
Mayo Clinic, NCCTG Find No Tie Between PTEN And Response To Breast Cancer Drug
ASCO Abstract #10504. Contrary to what many oncologists had thought, a tumor suppressor protein known as PTEN does not reduce the effectiveness of the breast cancer drug Herceptin, according to a study by Mayo Clinic and North Central Cancer Research Group (NCCTG) investigators. The study, which looked at tumors from 1,802 patients enrolled in the NCCTG N9831 clinical trial, found that patients with HER2-positive breast cancer and had either a loss of PTEN functioning or normal PTEN activity did equally well when Herceptin was added to chemotherapy to prevent breast cancer recurrence.
The researchers presented their findings during the American Society of Clinical Oncology Annual Meeting in Chicago."This is the largest study to date evaluating PTEN's presence or loss in the context of antiHER2 therapy, and we found no connection," says the study's lead investigator, oncologist Edith Perez, M.D., director of the Breast Clinic at Mayo Clinic in Jacksonville, Fla., and the Serene M. and Frances C. Durling Professor. "Our research team is very pleased to be able to test an important question in treatment of breast cancer and arrive at a definitive answer."
The researchers stained the samples for PTEN expression and linked that data with disease-free survival. They found that PTEN status did not impact disease-free survival significantly; there was only a slightly greater benefit of adding Herceptin for patients with PTEN-tumors.
Preclinical studies and some small patient studies had suggested that tumors with loss of PTEN expression would not benefit from Herceptin, Dr. Perez says. As a result, investigators were considering using PTEN biomarkers in clinical studies as a test of Herceptin resistance, and patients who tested positive for PTEN loss might then be offered other therapies, or invited to participate in clinical trials.
"We have all been interested in biomarkers that predict for benefit to antiHER2 therapy," Dr. Perez says, "but PTEN is not one that we should pursue further, based on our rigorous analysis."
The tumor samples examined in the study came from NCCTG N9831, a phase III randomized, multicenter clinical trial that tested adjuvant Herceptin given with, or following, chemotherapy with paclitaxel, compared with chemotherapy alone.
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