Geburtshilfe Frauenheilkd 2014; 74 - FV_08_02
DOI: 10.1055/s-0034-1388600

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

M Wallwiener 1, AD Hartkopf 2, S Riethdorf 3, J Nees 4, FA Taran 2, B Schönfisch 2, J Heil 1, C Sohn 1, K Pantel 3, A Trumpp 5, A Schneeweiss 4
  • 1Klinikum der Ruprecht-Karl-Univ. Heidelberg, Frauenheilkunde und Geburtshilfe, Heidelberg, Germany
  • 2Universitäts-Frauenklinik Tübingen, Tübingen, Germany
  • 3Abt. für Tumorbiologie Universität Hamburg Eppendorf, Hamburg, Germany
  • 4Nationales Zentrum für Tumorerkrankungen, Universitätsklinikum Heidelberg, Heidelberg, Germany
  • 5HI-STEM – Heidelberg Institute for Stem Cell Technology and Experimental Medicine, Heidelberg, Germany

Purpose: To retrospectively compare the expression of human epidermal growth factor receptor 2 (HER2) by the primary tumor, metastatic tissue, and circulating tumor cells (CTCs) and to analyze the potential impact of HER2 overexpression by CTCs on progression-free (PFS) and overall survival (OS) of patients with metastatic breast cancer (MBC).

Methods: CTC-positive (≥5 CTCs/7.5 ml peripheral blood; CellSearch®, Veridex) MBC patients aged > 18 years starting a new line of systemic treatment during 03/2010 – 07/2013 were eligible for inclusion. HER2 status was determined for CTCs (immunofluorescence) and primary (PRIM) and metastatic (MET) samples (immunocytochemistry). Data were analyzed using descriptive and nonparametric statistics.

Results: Included were 107 patients of median age (range) 57 (33 – 81). 37/107 (35%) patients were CTC-HER2-positive; 10/37 (27%) were PRIM-HER2-positive. 6/46 (13%) patients were MET-HER2-positive; 2/10 (20%) CTC-HER2-positive patients were MET-HER2-positive. 1/6 (17%) MET-HER2-positive patients was PRIM-HER2-positive. 100/107 (93%) patients were followed-up for a median period (95% confidence interval (CI)) of 28.5 (5.1 – 40.1) months. Kaplan-Meier analysis of PFS and OS by CTC-HER2 status revealed a significantly longer median PFS of CTC-HER2-positive patients (7.36 (4.70 – 13.67) months) compared with CTC-HER2-negative patients (4.34 (3.52 – 5.85) months) (p= 0.035). CTC-HER2-positive status was not associated with OS (13.67 (7.47 – 30.00) versus 8.74 (5.85 – 15.30) months) (p= 0.287).

Conclusions: HER2 status can change during the course of breast cancer, with important consequences for targeted treatment efficacy. CTC phenotyping may serve as an easy-to-perform, repeatable “liquid biopsy” to guide treatment decisions. The improved prognosis in CTC-HER2-positive patients may be due to effective targeted treatment.