New Assay May Increase Chance of Early Breast Cancer Detection

DALLAS—A new blood test technique to detect breast cancer cells may be 10- to 100-fold more sensitive than any current techniques, Jonathan W. Uhr, MD, of the University of Texas Southwestern Medical Center, Dallas, said at the Susan G. Komen Foundation’s National Grant Conference.

“Early diagnosis of breast cancer markedly increases the proportion of patients who will be cured,” Dr. Uhr said. “However, some small cancers detected by mammography may already have metastasized. It is, therefore, of critical importance to develop tests that will diagnose the disease at the earliest stage possible.”

To that end, Dr. Uhr and his colleagues have developed a test for detecting breast cancer cells that are shed in the blood from very small tumors. “These cells probably die in the circulation when the tumor is at an early stage and do not go on to metastatic growth,” he said. “However, they can be used to detect breast cancer.”

Using the assay, the researchers have found blood tumor cells in 15 of 16 patients with early-stage breast cancer.

“The test is based on the principle that breast carcinoma is of epithelial origin while the blood elements are not. Hence, antibodies against molecules on the blood elements and antibody against molecules on epithelial cells can distinguish the carcinoma cells from the normal blood elements,” Dr. Uhr said.

The test is done by coating submicro-scopic iron particles with an antibody to an epithelial cell surface molecule and using very strong magnets to “purify” the rare epithelial cells 10,000-fold (see Figure). The enriched mixture is passed through a machine that uses a laser light beam to further distinguish red cells, white cells, and epithelial cells using antibodies to each and different dyes that fluoresce differently as they pass through the laser light beam. “This technique can detect a single epithelial cell in a tablespoonful of blood,” Dr. Uhr said.

The technique is expected to be useful in breast cancer detection at a very early stage and may also help determine which patients with early tumors need chemotherapy, whether surgery has completely removed the tumor, and whether tumor cells that persist in the blood represent growing metastases or a population of dying or nondividing tumor cells that may never cause a clinical recurrence.

“We are performing tests to give us a genetic ‘signature’ for the tumor cells so we can observe the genetic changes as the tumor evolves and make use of this information for genetic therapy in the future,” Dr. Uhr said.