Researchers find circulating tumor cells in long-term cancer survivors

DALLAS - Dec. 15, 2004 - Researchers at UT Southwestern Medical Center at Dallas have shown that some long-term breast-cancer survivors may have innate mechanisms to keep breast cancer at bay.

Their findings, published in the December issue of Clinical Cancer Research and available online, show that one-third of the longtime disease-free patients in the study had circulating tumor cells (CTCs).

The presence of CTCs is often associated with a higher risk of recurrence if they are found soon after a mastectomy. The UT Southwestern discovery that CTCs can be found in patients up to 20 years after mastectomy is notable because these patients have a very low risk of recurrence. After 20 years, the risk of recurrence rises to 20 percent of survivors, and scientists are still unsure why.

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Dr. Jonathan Uhr, professor in the Cancer Immunobiology Center and of microbiology and internal medicine at UT Southwestern Medical Center, and colleagues have shown that some long-term breast-cancer survivors may have innate mechanisms to keep the disease at bay. Their findings are published in the December issue of Clinical Cancer Research.

"Dormancy is a mysterious phenomenon that occurs in certain types of cancer," said Dr. Jonathan Uhr, lead author of the study and professor in the Cancer Immunobiology Center and of micro-
biology and internal medicine. "The term refers to a recurrence of cancer long after the tumor has been removed."

Based on his previous data gathered from mouse models of cancer dormancy, Dr. Uhr and colleagues used a stringent and sensitive set of tests to identify CTCs in women who had mastectomies and had been clinically cancer-free for at least seven years.

The investigators collected blood from 36 study participants. Of those, 13 breast-cancer survivors had CTCs, but the number of CTCs was low and remained low.

Because CTCs are short-lived, they must be constantly replenished, possibly from many tiny tumors somewhere in
the body.

Dr. Uhr said that there appears to be a precise balance between tumor cell replication and cell death. Those who stay healthy may have developed a way of keeping the size of the tumor cell population in check, making breast cancer a chronic illness in these patients, he said.

The next step, Dr. Uhr said, is to investigate the mechanisms for how the body and the cancer cells peacefully coexist. Such studies could reveal new ways to control cancer.

"It is also important to determine what changes are responsible for relapse," he said.  "If patients at risk for impending relapse can be identified, it may be possible to prevent recurrence with appropriate therapy."

Other UT Southwestern contributors to this study included Drs. Debasish TripathyEugene Frenkel and Barbara Haley, all professors of internal medicine; Dr. James Huth, chairman of surgical oncology; Dr. Marilyn Leitch, professor of surgical oncology; Dr. David Euhus, associate professor of surgical oncology; Drs. Songdong Meng and Jianqiang Wang, postdoctoral researchers in the Cancer Immunobiology Center; and Nancy Lane, research scientist in the Cancer Immunobiology Center.

Researchers at UT M.D. Anderson Cancer Center in Houston, the Dallas Breast Center, Vysis Inc., Washington University in St. Louis, the Wistar Institute in Philadelphia, Immunicon Corp. and the University of Tubingen in Germany also contributed to the study, which was funded by the Nasher Cancer Research Program.

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Media Contact: Megha Satyanarayana or Scott Maier
(214) 648-3404
e-mail: megha.saty@utsouthwestern.edu
Scott.maier@utsouthwestern.edu

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