title: HER2 status of circulating tumor cells in patients with metastatic breast cancer: a prospective, multicenter trial.
abstract: There is a growing body of evidence that HER2 status can change during disease recurrence or progression in breast cancer patients. In this context, re-evaluation of HER2 status by assessment of HER2 expression on circulating tumor cells (CTCs) is a strategy with potential clinical application. The aim of this trial was to determine the HER2 status of CTCs in metastatic breast cancer patients comparing two CTC assays. A total of 254 patients with metastatic breast cancer from nine German university breast cancer centers were enrolled in this prospective study. HER2 status of CTCs was assessed using both the FDA-approved CellSearch® assay and AdnaTest BreastCancer™. Using the CellSearch assay, 122 of 245 (50%) patients had ≥5 CTCs, and HER2-positive CTCs were observed in 50 (41%) of these patients. Ninety of 229 (39%) patients were CTC positive using AdnaTest BreastCancer, and HER2 positivity rate was 47% (42 of 90). The rate of breast cancer patients with HER2-negative primary tumors but HER2-positive CTCs was 32% (25 of 78) and 49% (28 of 57) using the CellSearch assay and AdnaTest BreastCancer, respectively. Considering only those patients who had CTCs on both tests (n = 62), concordant results regarding HER2 positivity were obtained in 50% of the patients (31/62) (P = 0.96, κ = -0.006). HER2-positive CTCs can be detected in a relevant number of patients with HER2 negative primary tumors. Therefore, it will be mandatory to correlate the assay-dependent HER2 status of CTCs to the clinical response on HER2-targeted therapies.
authors.affiliation: Department of Gynecology and Obstetrics, University of Tübingen, Calwer Strasse 7, 72076, Tübingen, Germany. tanja.fehm@med.uni.tuebingen.de
authors.forename: Tanja
authors.initials: T
authors.lastname: Fehm
authors.forename: Volkmar
authors.initials: V
authors.lastname: Müller
authors.forename: Bahriye
authors.initials: B
authors.lastname: Aktas
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Janni
authors.forename: Andreas
authors.initials: A
authors.lastname: Schneeweiss
authors.forename: Elmar
authors.initials: E
authors.lastname: Stickeler
authors.forename: Claus
authors.initials: C
authors.lastname: Lattrich
authors.forename: Christian R
authors.initials: CR
authors.lastname: Löhberg
authors.forename: Erich
authors.initials: E
authors.lastname: Solomayer
authors.forename: Brigitte
authors.initials: B
authors.lastname: Rack
authors.forename: Sabine
authors.initials: S
authors.lastname: Riethdorf
authors.forename: Christoph
authors.initials: C
authors.lastname: Klein
authors.forename: Christian
authors.initials: C
authors.lastname: Schindlbeck
authors.forename: Kerstin
authors.initials: K
authors.lastname: Brocker
authors.forename: Sabine
authors.initials: S
authors.lastname: Kasimir-Bauer
authors.forename: Diethelm
authors.initials: D
authors.lastname: Wallwiener
authors.forename: Klaus
authors.initials: K
authors.lastname: Pantel
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000556:secondary* / Q000628:therapy; D018572:Disease-Free Survival; D005260:Female; D005455:Fluorescent Antibody Technique; D005858:Germany; D006801:Humans; D009360:Neoplastic Cells, Circulating / Q000737:chemistry* / Q000473:pathology*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012334:RNA, Neoplasm / Q000097:blood; D011933:Reagent Kits, Diagnostic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000097:blood* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D012334:RNA, Neoplasm; D011933:Reagent Kits, Diagnostic; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human