A high level of circulating tumor cells (CTCs) ? cells that have detached from a tumor and are circulating in the body through the blood ? are an independent prognostic marker in metastatic breast cancer as first-line therapy.  In addition, persistence of high CTC level during therapy was found to be an early marker of poor outcome. These are some conclusions from a large French trial.
?This is the largest, prospective series validating the prognostic value of CTCs in first-line chemotherapy metastatic breast cancer, independently from serum tumor markers for overall survival,? said Jean-Yves Pierga, M.D., Ph.D., professor of the medical oncology department, Institut Curie and Universit? Paris Descartes, France. ?Persistence of a high level of CTCs before the second cycle of chemotherapy was a strong and early predictive marker of poor outcome.?
Breast cancer can metastasize from a primary tumor in the breast to distant organs, such as the liver, lungs or bone, through the blood. New techniques have allowed for the detection of metastasis by testing blood for CTCs.
Previous research has not established that routine use of CTC measurements can improve patient outcomes, therefore, it is not currently a recommended practice, said Pierga.
The researchers prospectively tested CTCs as an outcome predictor compared with serum tumor markers in metastatic breast cancer patients treated by first-line chemotherapy. Serum tumor markers are proteins or glycoproteins released into the blood; however, tumor markers only indirectly reflect the presence of cancer and can be associated with dead cells, according to Pierga. In fact, some breast cancers can metastasize without any increase in tumor serum markers.
This study included 267 patients with metastatic breast cancer who were receiving first-line chemotherapy and had undergone assessment for three tumor markers: CA 15.3, CEA and LDH. Patients were enrolled in one of five cancer centers in France between June 2007 and Sept. 2009, and were followed for a median of 16 months.
Sixty-five percent of the patients had one or more CTCs; 44% had five or more CTCs. Of the measured tumor markers, 64% of patients had high CA 15.3, 51% had high CEA and 45% had high LDH.
High CTC levels were predictive of poor progression-free survival and overall survival, independent of serum tumor markers. Evaluation of serum tumor markers showed that baseline levels of CA 15.3, CEA and LDH were prognostic for poor progression-free survival, but only LDH was prognostic for overall survival. CTCs were highly associated with tumor markers, tumor burden, performance status, and number of metastatic sites, but were also independent of tumor biology, such as HER2 status, or grade of cancer.
?CTCs add an independent prognostic marker in metastatic breast cancer at first-line chemotherapy, and an early predictive marker of clinical benefit after one cycle of chemotherapy,? Pierga noted.
The trial was the largest trial to-date validating the prognostic value of CTC in first line chemotherapy metastatic breast cancer. A prospective multicenter randomized trial (CIRCE01) to assess the use of CTC-levels to modify treatment after second line chemotherapy is ongoing.
 Cristofanilli M, Budd GT, Ellis MJ, Stopeck A, Matera J, et al. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med. 2004 Aug 19;351(8):781-91
 Bidard FC, Mathiot C, Delaloge S, Brain E, Giachetti S, de Cremoux P, Marty M, Pierga JYSingle circulating tumor cell detection and overall survival in nonmetastatic breast cancer. Ann Oncol. 2010 Apr;21(4):729-33. Epub 2009 Oct 22.
For more information:
Pierga J-Y, Bachelot T, Delaloge S, Brain E, Campone M et al. [S6-6] High Independent Prognostic and Predictive Value of Circulating Tumor Cells in a Large Prospective Multicenter Trial Including Serum Tumor Markers in First Line Chemotherapy Metastatic Breast Patients. Presented on Saturday, December 11, 2010 4:15 PM (General Session 6); 33rd Annual CTRC-AACR San Antonio Breast Cancer Symposium
Pierga J-Y, Bidard F-C, Petit T, Delozier T, Ferrero J-M, et al. [PD04-07] Monitoring Circulating Tumor Cells (CTC) and Circulating Endothelial Cells (CEC) during Neoadjuvant Combination of Trastuzumab and Bevacizumab with Chemotherapy in HER2 Overexpressing Inflammatory Breast Cancer (IBC): An Ancillary Study of BEVERLY 2 Multicenter Phase II Trial. Presented on Friday, December 10, 2010 7:00 AM Poster Discussion 4: CTCs and DTCs (7:00 AM-9:00 AM); 33rd Annual CTRC-AACR San Antonio Breast Cancer Symposium.
Photo by ? SABCS/Todd Buchanan 2010