Jefferson and Burnham Institute scientists find a novel protein may predict long-term survival for women with early-stage breast cancer

December 06, 1999

Researchers at Jefferson Medical College believe they've found a novel protein "marker" that may predict the long-term survival of women with early breast cancer. They've shown that high levels of the protein BAG-1 correlate with a better chance of living disease-free longer and living longer overall.

Bruce C. Turner, M.D., Ph.D., assistant professor of radiation oncology at Thomas Jefferson University in Philadelphia, John C. Reed, M.D., Ph.D., Scientific Director of the Burnham Institute in La Jolla, and their colleagues at Yale University looked at 116 women with early-stage breast cancer, following them for an average of more than 12 years.

They found that a woman in this group whose breast tumor carries high amounts of BAG-1 protein had an overall 10-year survival of 81 percent. A similar woman whose tumor did not have BAG-1 had, on average, only a 50 percent chance of living 10 years.

"The difference in survival between these patients' groups is quite large and we think we have come up with a novel marker that may be an important diagnostic test for physicians to predict metastatic disease," says Dr. Turner. The researchers have also developed immunohistochemical and antibody techniques to isolate the protein. The finding "may influence subsequent therapy by suggesting that these women may need more intensive treatments such as high-dose chemotherapy, hormonal therapy or concurrent radiation and chemotherapy," he says.

Dr. Turner presents the research findings Dec. 8 at the 22nd Annual San Antonio Breast Cancer Symposium.

The scientists tested tumor tissue from each woman in the group, measuring levels of BAG-1, a protein that inhibits apoptosis, or programmed cell suicide. They found that compared to other potential cancer markers, such as p53, estrogen receptors, Her2/Neu, the disease "stage," and Bcl-2, another anti-apoptosis gene that predicts for survival, BAG-1 was best able to predict survival after 10 years.

"We were surprised that it seems a better indicator than other markers, and encouraged by the potential implications of these results in terms of treating early-stage breast cancer patients, especially those who have negative lymph nodes, because for those patients the use of high-dose chemotherapy and other therapies remains controversial," Dr. Turner says.

"If we can identify women with negative lymph nodes who are risk for developing metastatic disease using this novel marker, it might be reasonable to treat them with chemotherapy. That may not be case for patients with high levels of BAG-1.

"The important finding from this study is that BAG-1 is an important predictor of survival in patients who have pathologically negative lymph nodes and are at a low risk for developing metastatic disease," he says. "It's frequently difficult to make decisions regarding therapy for these women. Now we know that women with negative lymph nodes and low levels of BAG-1 are at risk of developing metastatic disease and may be good candidates for aggressive cancer treatments. This biomarker is not only a marker for survival in breast cancer patients, but more importantly, it's a marker for survival of women with negative lymph nodes. It's independent of lymph node status."

The Burnham Institute's Dr. Reed believes "BAG-1 really seems to provide a powerful new marker for identifying women with early stage breast cancers who are likely to enjoy long survival, separating them from those who are at high risk of metastatic disease and death."

The next step, Drs. Turner and Reed say, is to perform larger, prospective studies, looking at thousands of women to validate the finding that this marker may be one of the most powerful predictors of survival for women with breast cancer.

Thomas Jefferson University

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