Circulating tumor cells in HER2-positive metastatic breast cancer patients: a valuable prognostic and predictive biomarker

Yi Liu,Bing Liu,Qian Liu,Shaohua Zhang,Shikai Wu,Tao Wang,Zhiyuan Hu,Zefei Jiang,Li Bian,Haixu Hu,Sha Li

doi:10.1186/1471-2407-13-202

Abstract

BackgroundThis study was initiated to investigate the prognostic significance of circulating tumor cell (CTC) enumeration and the predictive value of CTC HER2 expression for efficient anti-HER2 therapy in HER2-positive metastatic breast cancer (MBC) patients.MethodsSixty HER2-positive MBC patients were enrolled in the present study. Before the initiation of systemic treatment, CTCs from 7.5 ml of blood were analyzed using the CellSearch system. The progression-free survival (PFS) of the patients was estimated using Kaplan-Meier survival curves.ResultsCTCs were detected in 45% (27/60) of the patients, who had shorter median PFS than those without CTCs (2.5 vs. 7.5 months, P = 0.0125). Furthermore, referring to the standard HER2 testing that uses immunohistochemistry (IHC), we proposed a CTC HER2-positive criterion, defined as >30% of CTCs over-expressing HER2. Among patients undergoing anti-HER2 therapy, those with HER2-positive CTCs had longer PFS (8.8 vs. 2.5 months, P = 0.002). Among patients with HER2-positive CTCs, the median PFS for those receiving anti-HER2 therapy was significantly longer than those who were not (8.8 vs. 1.5 months, P = 0.001). Notably, up to 52% (14/27) of the HER2-positive patients were CTC HER2-negative, and anti-HER2 therapy did not significantly improve the median PFS in these patients (2.5 vs. 0.9 months, P = 0.499).ConclusionsOur findings underscore the necessity of a comprehensive CTC analysis, which may provide valuable prognostic and predictive information for optimizing individually tailored therapies in HER2-positive MBC patients. To test this idea, additional large cohort, multi-center and prospective clinical trials are needed.

Highlights

This study was initiated to investigate the prognostic significance of circulating tumor cell (CTC) enumeration and the predictive value of Circulating tumor cells (CTCs) Human epidermal growth factor receptor 2 (HER2) expression for efficient anti-HER2 therapy in HER2-positive metastatic breast cancer (MBC) patients
≤12 months >12 months shown in Additional file 2: Table S2, CTCs were detected in 45% (27/60) of the HER2-positive patients, and the CTC count ranged from 1 to 1140 with a mean value of 68
In this study, we found that CTC enumeration with a cut-off of ≥1 but not ≥5 CTCs could serve as a useful prognostic factor for HER2-positive MBC patients

Summary

Introduction

This study was initiated to investigate the prognostic significance of circulating tumor cell (CTC) enumeration and the predictive value of CTC HER2 expression for efficient anti-HER2 therapy in HER2-positive metastatic breast cancer (MBC) patients. HER2 is considered to be a vital prognostic and predictive factor, and treatment of HER2-positive patients remains one of the great therapeutic challenges in metastatic breast cancer (MBC). Previous studies have demonstrated that there are inconsistencies in HER2 expression between primary tumors and their metastases [10,11] Such inconsistencies indicate that tumor cells are under constant evolvement or clonal selection and that the detected HER2 status may not necessarily reflect the patients’ real-time phenotypes. It is critical to discover more precise prognostic marker and real-time methods for HER2 testing to optimize individualized therapeutic regimens for HER2-positive MBC patients

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Results

Discussion

Conclusion