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. 2015 May 14:15:403.
doi: 10.1186/s12885-015-1423-6.

The impact of HER2 phenotype of circulating tumor cells in metastatic breast cancer: a retrospective study in 107 patients

Markus Wallwiener  1 , Andreas Daniel Hartkopf  2 , Sabine Riethdorf  3 , Juliane Nees  4 , Martin Ronald Sprick  5 , Birgitt Schönfisch  6 , Florin-Andrei Taran  7 , Jörg Heil  8 , Christof Sohn  9 , Klaus Pantel  10 , Andreas Trumpp  11   12 , Andreas Schneeweiss  13   14
Affiliations

The impact of HER2 phenotype of circulating tumor cells in metastatic breast cancer: a retrospective study in 107 patients

Markus Wallwiener et al. BMC Cancer. .

Abstract

Background: In metastatic breast cancer (MBC), antigen profiles of metastatic tissue and primary tumor differ in up to 20 % of patients. Reassessment of predictive markers, including human epidermal growth factor receptor 2 (HER2) expression, might help to optimize MBC treatment. While tissue sampling is invasive and often difficult to repeat, circulating tumor cell (CTC) analysis requires only a blood sample and might provide an easy-to-repeat, real-time "liquid biopsy" approach. The present retrospective study was conducted to compare HER2 expression in primary tumors, metastatic tissue, and circulating tumor cells (CTCs) from MBC patients and to analyze the potential impact of HER2 overexpression by CTCs on progression-free (PFS) and overall survival (OS) in MBC.

Methods: CTC-positive (five or more CTCs/7.5 mL blood; CellSearch®, Janssen Diagnostics) MBC patients starting a new line of systemic treatment were eligible for the study. HER2 status of CTCs was determined by immunofluorescence (CellSearch®). HER2 status of primary (PRIM) and metastatic (MET) tumor tissue was determined by immunohistochemistry. Data were analyzed using descriptive statistics and Kaplan-Meier plots.

Results: One hundred seven patients (median age (range) 57 (33-81) years) were included. 100/107 (93%) patients were followed-up for a median [95% confidence interval (CI)] of 28.5 [25.1-40.1] months. Of 37/107 (35%) CTC-HER2-positive patients only 10 (27%) were PRIM-HER2-positive. 6/46 (13%) patients were MET-HER2-positive; only 2/10 (20%) CTC-HER2-positive patients were MET-HER2-positive. Overall accuracy between CTC-HER2 expression and PRIM-HER2 and MET-HER2 status was 69% and 74%, respectively. Kaplan-Meier plots of PFS and OS by CTC-HER2 status revealed significantly longer median [95% CI] PFS of CTC-HER2-positive versus CTC-HER2-negative patients (7.4 [4.7-13.7] versus 4.34 [3.5-5.9] months; p = 0.035). CTC-HER2-positive status showed no significant difference for OS (13.7 [7.7-30.0] versus 8.7 [5.9-15.3] months; p = 0.287).

Conclusions: HER2 status can change during the course of breast cancer. CTC phenotyping may serve as an easy-to-perform "liquid biopsy" to reevaluate HER2 status and potentially guide treatment decisions. Further, prospective studies are needed.

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Figures

Fig. 1
Fig. 1
Patient flow through the study
Fig. 2
Fig. 2
Kaplan–Meier plots of progression-free survival (a) and overall survival (b) of CTC-positive (≥5 CTCs/7.5 mL blood) MBC patients by CTC-HER2 status
See this image and copyright information in PMC

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