Researchers develop blood test that can detect genetic changes in progressive breast cancer

06/04/04



Dr. Jonathan Uhr and his colleagues at UT Southwestern have developed a blood test that can detect overexpression of a certain gene found in circulating cells associated with breast cancer.

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DALLAS – June 7, 2004 – Researchers at UT Southwestern Medical Center at Dallas have developed a blood test that can detect amplification of a certain gene found in circulating cells associated with breast cancer.

If further clinical studies bear out its effectiveness, researchers say the blood test could be used as a standard operating procedure to monitor genetic changes for which a treatment is available.

"Cancer is a moving target, and the oncologist has to know which bullet to put in his gun," said Dr. Jonathan Uhr, professor of microbiology and internal medicine in the Cancer Immunobiology Center at UT Southwestern and senior author of the study. "Obtaining repeated blood samples is a safe and routine procedure, and this test can help the oncologist determine whether a new genetic change has become dominant and calls for a specific treatment for that change."

Their work will appear in an upcoming issue of the Proceedings of the National Academy of Sciences and is currently available online.

The researchers developed a blood test to optimize the detection and characterization of circulating cancer cells shed from a primary tumor. This is done by matching the cells' genetic abnormalities with the parent tumor.

The test can detect one circulating tumor cell in 10 million white blood cells, said Dr. Uhr.

The research augments previous work by UT Southwestern researchers to determine if patients whose primary tumor did not have amplification of the gene HER-2 could acquire amplification if the tumor recurred and progressed. Using the new blood test to examine the circulating tumor cells from growing tumors, initial indications are this amplification eventually can occur, Dr. Uhr said.

Dr. Uhr says that in a patient whose primary tumor is classified as HER-2 gene non-amplified, a minute number of tumor cells actually may be HER-2 amplified. With time and selective pressures, this small population expands and becomes the predominant one.

Overexpression of the HER-2 gene occurs in about 20 percent to 25 percent of breast-cancer patients. Prognosis is poor, as the cancer cells often resist radiation therapy and almost all drugs.

However, studies have shown that the drug Herceptin (an antibody to HER-2) can treat tumors with HER-2 amplification by itself in 25 percent of patients and in 50 percent when combined with chemotherapy. The antibody binds to the molecules that are produced by the HER-2 gene and reside on the cancer cells' surface. The drug neutralizes their effect with far fewer side effects than conventional chemotherapy.

By utilizing this blood test to determine HER-2 gene amplification in circulating cancer cells, doctors may be able to provide Herceptin to certain patients who have acquired such amplification. At present, HER-2 amplification is only diagnosed in the primary tumor.

"The implications of tumor evolution over the course of treatment are significant," said Dr. Debasish Tripathy, professor of internal medicine and contributing author. "A better understanding of this process will not only allow us to use available drugs in a more individualized fashion but also may point to new therapeutic approaches." Dr. Tripathy heads the Komen/UT Southwestern Breast Cancer Research Program.

The next step is to evaluate patients whose circulating tumor cells have acquired HER-2 gene amplification to determine if these cells are reflecting the genetic status of the recurrent tumor, said Dr. Uhr. For the blood test to be considered worthwhile, research also must show that therapy with Herceptin alone or in addition to a chemotherapeutic agent can cause remissions in a significant number of patients.

Source: Eurekalert & others

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