Real-time HER2 status detected on circulating tumor cells predicts different outcomes of anti-HER2 therapy in histologically HER2-positive metastatic breast cancer patients.

Shaohua Zhang,Zefei Jiang,Massimo Cristofanilli,Bing Liu,Tao Wang,Lei Li,Haixu Hu,Chunhong Xu,Li Bian,Yi Liu

doi:10.1186/s12885-016-2578-5

Shaohua Zhang, Zefei Jiang + Show 8 more

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https://doi.org/10.1186/s12885-016-2578-5

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Abstract

BackgroundThis study was initiated to investigate the difference in HER2 status between tumor tissue and circulating tumor cells (CTCs), as well as the predictive value of CTC HER2 status for predicting the outcomes of anti-HER2 therapy in histologically HER2-positive metastatic breast cancer (MBC) patients.MethodsHER2 expression on CTCs was detected using a CellSearch system within 7 days before a new line of anti-HER2 therapy was begun. According to the criterion proposed in our previous report, patients were defined as CTC HER2-positive or -negative. After close follow-up, the correlation between CTC HER2 status and the outcome of the treatment was evaluated by statistical analysis.ResultsCTCs were detected in 57.4 % (58/101) of the patients. Notably, 62.1 % (36/58) of these patients had an inconsistent HER2 status between their tissue and CTCs. The discordant rate may correlate with the time interval between histological and CTC HER2 testing and is more likely to occur in the subgroup of patients with an interval of > 1 year than in those with an interval < 1 year (70.7 % vs. 41.2 %, P = 0.043). For PFS, positive HER2 status on CTCs was shown to be a valuable predictor, both in univariate (HR = 0.321, 95%CI, 0.156–0.62, P = 0.0011) and multivariate (HR = 0.383, 95%CI, 0.166–0.831, P = 0.019) Cox regression analysis. Meanwhile, Kaplan-Meier survival curves revealed that the median PFS of CTC HER2-positive patients was significantly longer than CTC HER2-negative ones (8.5 vs. 3.5 months, P < 0.001).ConclusionsHER2 status on CTCs was different from that of tumor tissues and predicted a different outcome of the patients’ anti-HER2 therapy. This difference may be correlated with the time interval between tissue and CTC HER2 testing, indicating the necessity of real-time HER2 analysis for histologically HER2-positive MBC patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2578-5) contains supplementary material, which is available to authorized users.

Highlights

This study was initiated to investigate the difference in Human epidermal growth factor receptor 2 (HER2) status between tumor tissue and circulating tumor cells (CTCs), as well as the predictive value of Circulating Tumor Cells (CTC) HER2 status for predicting the outcomes of anti-HER2 therapy in histologically HER2-positive metastatic breast cancer (MBC) patients
Patient characteristics and CTC detection From September 2010 to November 2013, 101 histologically HER2-positive MBC patients with a median age of 48 years were enrolled in the present study. Those patients were divided into CTC positive and negative group, and their characteristics were shown in Additional file 1: Table S1
The patient characteristics of the 2 groups are listed in Table 1 and indicate that negative CTC HER2 status may be found in patients considered to be ER-and/or PR-positive (P = 0.014)

Summary

Introduction

This study was initiated to investigate the difference in HER2 status between tumor tissue and circulating tumor cells (CTCs), as well as the predictive value of CTC HER2 status for predicting the outcomes of anti-HER2 therapy in histologically HER2-positive metastatic breast cancer (MBC) patients. The over-expression of this 185 kDa transmembrane tyrosine kinase receptor or the amplification of this gene located on human chromosome 17q21 results in what is called the HER2-positive molecular subtype of breast cancer that occurs in approximately 20 % of patients [2, 3] and is associated with worse outcome. The introduction of anti-HER2 therapy, such as trastuzumab, lapatinib, pertuzumab, and trastuzumab emtansine (T-DM1), has resulted in dramatic improvements in outcome of primary and metastatic disease [4,5,6,7]. A cohort of patients with HER2-positive disease can develop disease recurrence or progression during trastuzumab or other HER-2 targeted therapy raising questions regarding the resistance mechanisms and most appropriate diagnostic modalities for treatment selection

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