The presence of one to four circulating tumor cells (CTCs) in the blood of early-stage breast cancer patients almost doubled patient?s risk of cancer relapse and death, and five or more CTCs increased recurrence by 400% and death by 300%, according to Phase III results of the SUCCESS trial. These cells were found in patients after surgery but before chemotherapy treatment.

Results of this study were presented at the 33rd Annual CTRC-AACR San Antonio Breast Cancer Symposium, held Dec. 8-12, 2010, and demonstrate the value of CTCs in early breast cancer, independent of estrogen-receptor or HER2 status and before use of adjuvant therapy.

The benefit of using CTCs to predict risk for recurrence and death in metastatic breast cancer patients has been shown in a number of studies, and use of a CTC test in metastatic breast cancer has been approved by the Food and Drug Administration (FDA).

The CTCs found in this study are likely evidence that a tumor is shedding breast cancer cells, said lead researcher Brigitte Rack, M.D., head of the department of gynecological oncology at the Women?s Hospital at the University of Munich, Germany. ?The CTCs might have been released from the primary tumor before these patients underwent surgery, and the expression of stem cell markers on disseminated tumors cells has been shown by several groups.? Survival of these CTCs after chemotherapy further suggests they are cancer stem cells, Rack added.

Researchers with this study are testing the effectiveness of two different chemotherapy regimens and extended adjuvant bisphosphonate treatment in early breast cancer. SUCCESS? efficacy data are expected to be released next year.

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The SUCCESS study compares the disease-free survival after randomization in patients treated with 3 cycles of Epirubicin (100 mg/m2)-Fluorouracil(500)-Cyclophosphamide (500, FEC)-chemotherapy, followed by 3 cycles of Docetaxel (100 mg/mg2, D) versus 3 cycles of FEC, followed by 3 cycles of Gemcitabine (1,000mg/m2 d1,8)-Docetaxel (75 mg/m2)(DG).

All patients CTC were analyzed using the CellSearchSystem (Veridex, USA). 23 ml of peripheral blood were drawn after R0-resection of the primary tumor but before the start of adjuvant systemic treatment. After immunomagnetic enrichment with an anti-Epcam-antibody, cells were labeled with anti-Ck8/18/19 and anti-CD45 antibodies to distinguish between epithelial cells and leukocytes. Patients were followed for a median of 35 months. Univariate and multivariable proportional hazards models were estimated to assess the prognostic significance of CTC for disease-free and overall survival. Patients with evidence of at least 1 CTC were counted as positive.

Results of this study showed that 21.5% of patients had one or more CTCs in their blood before the start of adjuvant treatment. These patients were more frequently node-positive, but no other linkage could be made with tumor size or grade or HER2 status.

Breast cancer recurred in 114 patients, and 66 patients died. Being CTC-positive was a significant independent predictor for both disease-free and overall survival. Patients with one to four CTCs had an 88% increased risk of early breast cancer recurrence and a 91% increased risk of death from breast cancer, according to Rack.

Prognosis was worse in patients with five or more CTCs; these patients had a fourfold risk of cancer recurrence and a threefold risk for death from the disease.

?Our study suggests testing CTCs may prove to be important to help individualize therapy for early-stage breast cancer where no measurable tumor is present,? she said. ?Patients who seem to be at high risk due to CTC may benefit from additional treatment options, and those that don?t have CTCs may be spared side effects of some treatments.?

She added, however, that prospectively randomized trials are necessary to show an improvement of survival based on CTC diagnostics. Trials testing this notion are either ongoing or about to start in Europe and the United States, according to Rack.

The SUCCESS trial, which enrolled 2,026 patients, was designed to look for CTCs and tumor markers in the blood using CellSearch technology at four different time points: before chemotherapy, after chemotherapy, after two years of endocrine/zoledronic acid treatment, and after five years of endocrine/zoledronic acid treatment.

For more information:
Rack B, Schindlbeck C, Andergassen U, Lorenz R, Zwingers T, et al. [S6-5] Prognostic Relevance of Circulating Tumor Cells in the Peripheral Blood of Primary Breast Cancer Patients. Saturday, December 11, 2010 4:00 PM (General Session 6); 33rd Annual CTRC-AACR San Antonio Breast Cancer Symposium.

Photo by ? SABCS/Todd Buchanan 2010

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