Circulating tumor cells correlate with recurrence in early disease

December 13, 2010
Ed Susman

The SUCCESS adjuvant therapy trial enrolled 2,026 women with primary breast cancer and no clinical evidence of metastatic disease. Disease-free survival at three years was 88.1% in women with one or more circulating tumor cells (CTCs) in their peripheral blood before undergoing chemotherapy compared with 93.7% in women with no CTCs.

SAN ANTONIO-Women with early-stage breast cancer and a high circulating tumor cell (CTC) count may be at greater risk of disease recurrence and death, according to the results of the SUCCESS* trial. “The SUCCESS trial confirms the independent prognostic relevance of circulating tumor cells in early breast cancer in a large patient cohort,” said trial investigator Brigitte Rack, MD, head of the department of gynecological oncology at the Women’s Hospital at the University of Munich, Germany.

In the SUCCESS trial, Dr. Rack and colleagues enrolled 2,026 women with primary breast cancer and no clinical evidence of metastatic disease. Following complete tumor dissection and before chemotherapy, blood was drawn and analyzed through the CellSearch system. During the median 35-month follow-up, 114 women recurred and 66 died of breast cancer.

Among those who were positive for CTCs, counts ranged from one to 827 cells. About 2.3% of women in the study had more than five CTCs. Disease recurred in 41 of 436 CTC-positive women and 78 of 1,589 CTC-negative women. In women with one or more CTCs, disease-free survival at three years was 88.1% compared with 93.7% in women with no CTCs (P < .0001).

Multivariate analysis for disease-free survival showed greater risk of recurrence with higher CTC counts, Dr. Rack said. The hazard ratios adjusted for treatment were 1.878, 2.825, and 4.035, respectively, for women with no CTCs compared to women with one or more CTCs, women with no CTCs or only one cell compared to women with two or more CTCs, and women with zero to four CTCS compared with women with five or more CTCs (all comparisons, P < .05) (SABCS 2010 abstract S6-5). Dr. Rack also reported that three-year overall survival was improved in women with no CTCs compared to those who were CTC positive (97.3% vs 93.2%, P =.0002). There were 23 deaths among the 436 CTC-positive women compared with 33 deaths among the 1,589 women who were CTC negative.

“Overall, circulating tumor cells were detected in 21.5% of early breast cancer patients before the start of adjuvant chemotherapy,” Dr. Rack said. “Presence of the cells predicted poor disease-free survival, distant disease-free survival, and overall survival.”

However, the questions remains as to what clinicians should do when CTCs are found. Dr. Rack suggested that CTC presence may indicate the need for more aggressive therapies. Early testing also may be advisable. “Our study suggests that testing for CTCs may prove to be important to help individualize therapy for early-stage breast cancer where no measurable tumor is present,” she said.

Commenting on the study was Minetta Liu, MD, director of translational breast cancer research at the Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC. Dr. Liu pointed out that there is still uncertainty as to the genesis of CTCs. There is speculation that CTCs break off from the main tumor, circulate for a time in the blood, and then become distant metastases. Another theory is that CTCs are simply bystanders that have no role in cancer progression at all.

“The key issue is that we really don’t know what CTCs are,” Dr. Liu said. “Although we can count some cells, what they are and where they come from remains to be determined.”

*SUCCESS = Simultaneous Study of Gemcitabine-Docetaxel Combination Adjuvant Treatment, as well as Extended Bisphosphonate and Surveillance trial