Abstract P2-08-09: Prognostic values of circulating tumor cell (CTC) enumeration and their clusters in advanced breast cancer
Authors: Ye Z , Mu Z , Wang C , Palazzo JP , Biederman L , Li B , Jaslow R , Avery T , Austin L , Yang H , Cristofanilli M 
Published: May 2016

Abstract
Background The enumeration of circulating tumor cells (CTCs) has been proven to have prognostic values in several solid tumors including breast cancer. It has been established that a cut-off of 5 CTCs in 7.5 ml of blood may significantly differentiate breast cancer patients with favorable and unfavorable survival. However, CTC enumeration has not been shown to further predict the prognosis in those patients with more than 5 CTCs in 7.5 ml of blood. There are several recent in vitro and in vivo studies suggesting that clusters of CTC can be identified in blood and those clusters may play an important role in tumor progression and metastasis. Few clinical studies have been reported to enumerate CTC clusters and evaluate their prognostic values. In the current study, we hypothesize that the enumeration of CTC clusters play an important role in the prognostication of advanced breast cancer patients by providing additional predictive performance independent of CTC enumeration.
Methods In an ongoing study of blood-based breast cancer biomarkers, we enrolled 114 patients with stages III and IV breast cancer. Among them, 68 patients had inflammatory breast cancer (IBC), an extremely aggressive form of breast cancer with a much lower survival rate than non-IBC breast cancer patients. The number of single CTCs and CTC clusters (two or more CTCs bound together) in 7.5 ml blood sample were counted using the CellSearch™ system (Janssen Diagnostic) at baseline study entry, and their associations with the progression-free survival (PFS) of patients were evaluated using Kaplan Meier curves and Cox proportional hazards modeling.
Results Baseline CTCs were detected in 67 (58.77%) patients. Thirty-five (30.70%) and 19 patients (16.67%) had elevated CTCs (≥5 CTCs/7.5 mL) and clusters, respectively. IBC patients had a slightly higher percentage of cluster (17.65%) compared to non-IBC patients (15.22%). Patients with elevated baseline CTC and cluster had worse PFS (log rank P, 0.0009 and 0.0035, respectively). Compared to patients with &lt; 5 CTC and without cluster, those patients with elevated CTC without cluster, and those with elevated CTC with cluster had an increasingly higher risk of disease progression with an hazard ratio [HR] of 1.93 (95% confidence interval [CI] 1.01-3.67) and 2.91 (1.54-5.50), respectively (P for trend = 0.001). Moreover, the combined analysis of baseline CTC and cluster enumerations showed similar effect when the analysis was restricted to IBC patients (HR 3.03, 95% CI 1.34-6.86).
Conclusion Baseline enumerations of both individual CTCs and CTC clusters predict PFS in advanced stage breast cancer patients. CTC clusters provide further prognostic value in patients with elevated CTC and their molecular characterizations may provide novel insights into the metastasis process.
Citation Format: Ye Z, Mu Z, Wang C, Palazzo JP, Biederman L, Li B, Jaslow R, Avery T, Austin L, Yang H, Cristofanilli M. Prognostic values of circulating tumor cell (CTC) enumeration and their clusters in advanced breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-08-09.