Abstract PD6-6: A pooled analysis of the prognostic relevance of circulating tumor cells in early breast cancer
Authors: WJ Janni, BK Rack, LMWW Terstappen, J-Y Pierga, T Fehm, C Hall, M Groot, F-C Bidard, F Meier-Stiegen, TWP Friedl, P Fasching, A Lucci
Journal: Cancer Research (2013)

Abstract Background: While there is unequivocal evidence regarding the prognostic relevance of circulating tumor cells (CTCs) in peripheral blood of patients (pts.) with metastatic breast cancer (BC), less data is available for the prognostic relevance at time of primary diagnosis. Methods: We conducted a pooled analysis with individual data of 3172 pts with non-metastatic (Stage I-III) BC from five academic institutions. Prevalence and number of CTCs in the peripheral blood were assessed at time of primary diagnosis using the FDA-approved CellSearch System (Veridex, USA). Patient outcomes were analyzed using univariate log-rank tests and multivariate Cox regressions. The median follow-up time was 61 months. Results: At least one CTC was detected in 20.2% of the pts. The presence of CTCs was associated with larger tumors, more axillary lymph node metastases, and higher histological tumor grade (all p &amp;lt; 0.005). The presence of CTCs was significantly related to poor progression-free (PFS, log-rank test, p &amp;lt; 0.001, hazard ratio [HR] 2.0) and overall survival (OS, p &amp;lt; 0.001, HR 2.6). Multivariate Cox regressions, including tumor size, nodal status, histological tumor grade, hormone receptor status and HER2 status, and CTC prevalence confirmed that the presence of CTCs was an independent prognostic factor for both poor PFS (HR 1.8) and OS (HR 2.1, both p &amp;lt; 0.001). In the univariate subgroup analysis concerning OS, the HR for pts. with positive HRS was 3.1 (p&amp;lt; 0.0001), and 2.0 (p = 0.001) for pts. with a negative HRS. The prognostic relevance of CTC status was similar for patients with HER2 negative and HER2 positive tumors (HR 2.6 and 2.5, respectively). The HR in CTC-positive pts. with HRS positive/HER2 positive tumors was 3.4 (p = 0.003). For patients with more than 3 CTCs, the hazard ratio for death was increased to 5.2 (1.5 - 2.8) in univariate and to 4.0 (2.6 - 6.2) in multivariate analysis. Cox Regression Analysis for Overall SurvivalVariableHazard ratio95% CIP-valueCTCs pos vs. neg2.1081.594 - 2.788&amp;lt;0.001Tumor grade 0.001G2 vs. G11.0730.489 - 2.3540.861G3 vs. G12.2391.028 - 4.8740.042Histological type 0.389lobular vs. ductal1.3200.865 - 2.0150.198other vs. ductal0.8980.498 - 1.6200.722Tumor stage &amp;lt;0.001T2 vs. T11.8531.301 - 2.6380.001T3 vs. T13.7062.310 - 5.947&amp;lt;0.001T4 vs. T13.5382.014 - 6.218&amp;lt;0.001Nodal stage &amp;lt;0.001N1 vs. N01.5471.081 - 2.2130.017N2 vs. N02.5381.660 - 3.879&amp;lt;0.001N3 vs. N03.8242.471 - 5.918&amp;lt;0.001Hormone receptor status pos vs. neg0.4020.294 - 0.550&amp;lt;0.001Her2 status pos vs. neg0.5790.407 - 0.8230.002Menopausal status post vs. pre1.3701.023 - 1.8340.035 Conclusions: In patients with early breast cancer, the presence of CTCs in peripheral blood is an independent predictor of poor progression-free and overall survival. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr PD6-6.