Abstract S6-5: Prognostic Relevance of Circulating Tumor Cells in the Peripheral Blood of Primary Breast Cancer Patients
Authors: Rack B , Schindlbeck C , Andergassen U , Lorenz R , Zwingers T , Schneeweiss A , Lichtenegger W , Beckmann MW , Sommer H , Pantel K , Friese K , Janni W 
Published: April 2011

The prognostic relevance of disseminated tumor cells in bone marrow of breast cancer patients at the time of primary diagnosis and during recurrence-free follow-up has been confirmed by large pooled analyses. Furthermore, circulating tumor cells (CTC) in peripheral blood have been shown as predictor of shortened progression-free and overall survival in metastatic disease. In view of the lack of data in early breast cancer, we evaluated whether the presence of CTC before the start of systemic adjuvant treatment increases the risk of subsequent relapse and death.

Patients and Methods The SUCCESS A-Study is an open-label randomized controlled, phase III study comparing the disease-free survival after randomisation 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). In 2026 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 labelled 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 In 21.5% of patients (n = 435) CTC were detected before the start of systemic treatment (median 1.3, range 1 - 827). Patients with CTC before treatment were more frequently node-positive (P&lt;0.001), but no correlation to tumor size, grading and HR-Status could be found. 114 recurrences occurred and 66 patients died of their disease. The presence of CTC before systemic treatment predicted poor disease-free (p &lt; 0.0001), distant disease-free survival (p &lt; 0.001) and overall survival (p = 0.0002). In multivariate analysis, detection of CTC before treatment was confirmed as independent predictor for both disease-free (HR 1.88) and overall survival (HR 1.91) next to tumor size, grading, lymph node involvement and hormone receptor status (p for all &lt; 0.05). Outcome of patients was correlated to the number of CTC. Prognosis was worst in patients with 5 CTC or more with a four-fold increased risk for recurrence and and a three-fold increased risk for death (HR 4.04 for DFS and 3.05 for OAS; p &lt; 0.05).

Conclusions This is the first study to prospectively demonstrate the prognostic relevance of CTC in peripheral blood of early breast cancer patients before the start of systemic treatment in a large patient cohort. CTC detection could serve as clinically useful prognostic marker and treatment monitoring tool and should be tested as indicator for secondary adjuvant treatment interventions within clinical trials.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr S6-5.