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Clinical Cancer Research Vol. 10, 8152-8162, December 15, 2004
© 2004 American Association for Cancer Research


Clinical Trials

Circulating Tumor Cells in Patients with Breast Cancer Dormancy

Songdong Meng1, Debasish Tripathy2, Eugene P. Frenkel2, Sanjay Shete4, Elizabeth Z. Naftalis3, James F. Huth3, Peter D. Beitsch5, Marilyn Leitch3, Susan Hoover3, David Euhus3, Barbara Haley2, Larry Morrison6, Timothy P. Fleming7, Dorothee Herlyn8, Leon W. M. M. Terstappen9, Tanja Fehm10, Thomas F. Tucker1, Nancy Lane1, Jianqiang Wang1 and Jonathan W. Uhr1

1 Cancer Immunobiology Center, 2 Department of Medicine, Komen Breast Cancer Center, and 3 Center for Breast Care, University of Texas Southwestern Medical Center, Dallas, Texas; 4 Department of Epidemiology, University of Texas M. D. Anderson Cancer Center, Houston, Texas; 5 Dallas Breast Center, Dallas, Texas; 6 Vysis, Inc., Downers Grove, Illinois; 7 Department of Surgery, University of Washington, St. Louis, Missouri; 8 Wistar Institute, Philadelphia, Pennsylvania; 9 Immunicon Corporation, Huntingdon, Pennsylvania; and 10 Department of Gynecology and Obstetrics, University of Tubingen, Tubingen, Germany

Purpose: The purpose of this study was to test the hypothesis that circulating tumor cells (CTCs) are present in patients many years after mastectomy without evidence of disease and that these CTCs are shed from persisting tumor in patients with breast cancer dormancy.

Experimental Design: We searched for CTCs in 36 dormancy candidate patients and 26 age-matched controls using stringent criteria for cytomorphology, immunophenotype, and aneusomy.

Results: Thirteen of 36 dormancy candidates, 7 to 22 years after mastectomy and without evidence of clinical disease, had CTCs, usually on more than one occasion. Only 1 of 26 controls had a possible CTC (no aneusomy). The statistical difference of these two distributions was significant (exact P = 0.0043). The CTCs in patients whose primary breast cancer was just removed had a half-life measured in 1 to 2.4 hours.

Conclusions: The CTCs that are dying must be replenished every few hours by replicating tumor cells somewhere in the tissues. Hence, there appears to be a balance between tumor replication and cell death for as long as 22 years in dormancy candidates. We conclude that this is one mechanism underlying tumor dormancy.




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