Abstract S6-5: Prognostic Relevance of Circulating Tumor Cells in the Peripheral Blood of Primary Breast Cancer Patients

Abstract

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<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 < 0.0001), distant disease-free survival (p < 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 < 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 < 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.

Persistence of Disseminated Tumor Cells in the Bone Marrow of Breast Cancer Patients Predicts Increased Risk for Relapse—A European Pooled Analysis

“…In contrast to patients with metastatic disease, much less information about the prognostic relevance of CTC in patients with early-stage disease is available (36). Studies using the CellSearch System or reverse transcriptase-PCRbased techniques have reported CTC persistence as an indicator of unfavorable outcome after completion of chemotherapy (37)(38)(39)(40). However, available studies comparing CTC and DTC analysis so far show only partially overlapping results, and the prognostic information from DTC seems to be higher than that from CTC (41)(42)(43).…”

A novel approach using telomerase-specific replication-selective adenovirus for detection of circulating tumor cells in breast cancer patients

“…Recently, Rack et al reported that CTCs were detected by the CellSearch assay in 21.5% of patients with stages I-III breast cancer using a cutoff value of C1 CTC per 23 ml blood and such patients had a significantly poorer disease-free survival and overall survival compared with those without CTCs [28]. The characteristics and clinical relevance of CTCs identified by the OBP-401 assay needs to be evaluated in EBC patients.…”

Prognostic Relevance of Circulating Tumor Cells in Blood and Disseminated Tumor Cells in Bone Marrow of Patients with Squamous Cell Carcinoma of the Oral Cavity

“…Furthermore, the clinical relevance of CTC detection was investigated in patients with various nonmetastatic cancer diseases, for example, in the course of translational research programs within neoadjuvant and adjuvant treatment studies (47,48). For patients with OSCC there are few studies investigating the dissemination of tumor cells after surgery (20,49), but there are no studies yet investigating this issue on the impact of metastases and survival.…”