Circulating tumor cells may have predictive, prognostic value

33rd Annual San Antonio Breast Cancer Symposium

SAN ANTONIO — The presence of circulating tumor cells may predict poorer outcomes among breast cancer patients, according to findings presented here.

Minetta C. Liu, MD, director of Translational Breast Cancer Research at the Lombardi Comprehensive Cancer Center at Georgetown University, moderated a press conference in which researchers presented results from three studies of circulating tumor cells.

“Circulating tumor cells are becoming a hot topic in the breast cancer field, but much is unknown about them,” she said. “They may circulate, lay dormant for a while and metastasize later.”

Possible etiologies are that they are disseminated cancer cells, cancer stem cells or bystander cells, according to Liu.

“They are rare cells in a dormant nonproliferative state,” she said. “Because they are largely unaffected by chemotherapy, biologics may be better at affecting them. They are difficult to isolate.”

Liu said that isolation of circulating tumor cells involves three steps: enrichment, detection and characterization. Detection of circulating tumor cells could improve diagnosis and prognosis in the future.

“Alterations in circulating tumor cell levels could help prognosis and determine whether therapy is working,” she said.

SUCCESS study

Birgitte Rack, MD, of the University of Munich in Germany, presented results of the SUCCESS study, which included 2,026 patients from 250 centers in Germany. Researchers analyzed 23 mL of blood from patients with primary breast cancer

“Circulating tumor cells were detected in 21.5% of early breast cancer patients before the start of adjuvant chemotherapy,” Rack said. She noted that the presence of these cells predicted poor DFS (P≤.001), distant DFS (P≤.001) and OS (P=.0002). Patients with at least one circulating tumor cell were counted as positive.

“These results confirm independent prognostic relevance of circulating tumor cells in the peripheral blood of primary breast cancer patients,” she said.

IC 2006-04 Study

Jean-Yves Pierga, MD, of the Curie Institute in Paris and the University of Paris, said that his group’s research was a hypothesis-driven study.

“We wanted to compare circulating tumor cell detection with usual seromarkers,” he said. “And we wanted to validate whether they predict better or worse outcomes in our country.”

Baseline data indicated that, compared with patients who had no circulating tumor cells, patients ≥5 circulating tumor cells had poorer PFS (P≤.0001). Similar results were observed for overall survival, according to Pierga.

“These trends held in multivariate analyses,” he said. He added that detection of these cells is not correlated with breast cancer subtypes.

“Though our results show that more circulating tumor cells are associated with poorer outcomes, the threshold of one cell is clinically relevant,” he said.

Results from MD Anderson

Hui Gao, PhD, a research scientist in the Department of Hematopathology at the University of Texas MD Anderson Cancer Center, presented results on the prognostic value of circulating tumor cells in the transplantation setting.

“After G-CSF mobilization and then aphaeresis, the cells were transfused back to the patient,” she said. “We used the flow cytometry method of staining for both epithelial and stem cell markers.”

The percentages of epithelial cells and cancer stem cells were counted to evaluate how they correlated with patient survival, according to Gao.

“Circulating tumor cell counts equal to or greater than five can predict outcome in high dose chemotherapy,” Gao said. “Patients without these cells had better overall survival compared with patients with five or more cells after transplant.

“These data suggest additional therapy may be needed to target epithelial-to-mesenchymal transition to achieve better clinical responses,” she said.

For more information:

• Gao H. #773.
• Pierga JY. #S6-6.
• Rack B. #S6-5. Presented at: The 33rd Annual San Antonio Breast Cancer Symposium; Dec. 8-12, 2010. San Antonio.

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