title: Prognostic Impact of HER2 and ER Status of Circulating Tumor Cells in Metastatic Breast Cancer Patients with a HER2-Negative Primary Tumor.
abstract: BACKGROUND
  Preclinical and clinical studies have reported that human epidermal growth factor receptor 2 (HER2) overexpression yields resistance to endocrine therapies. Here the prevalence and prognostic impact of HER2-positive circulating tumor cells (CTCs) were investigated retrospectively in metastatic breast cancer (MBC) patients with a HER2-negative primary tumor receiving endocrine therapy. Additionally, the prevalence and prognostic significance of HER2-positive CTCs were explored in a chemotherapy cohort, as well as the prognostic impact of the estrogen receptor (ER) CTC status in both cohorts.
  
  
  METHODS
  Included were MBC patients with a HER2-negative primary tumor, with ≥1 detectable CTC, starting a new line of treatment. CTCs were enumerated using the CellSearch system, characterized for HER2 with the CellSearch anti-HER2 phenotyping reagent, and characterized for ER mRNA expression. Primary end point was progression-free rate after 6 months (PFR6months) of endocrine treatment in HER2-positive versus HER2-negative CTC patients.
  
  
  RESULTS
  HER2-positive CTCs were present in 29% of all patients. In the endocrine cohort (n=72), the PFR6months was 53% for HER2-positive versus 68% for HER2-negative CTC patients (P=.23). In the chemotherapy cohort (n=82), no prognostic value of HER2-positive CTCs on PFR6months was observed either. Discordances in ER status between the primary tumor and CTCs occurred in 25% of all patients but had no prognostic value in exploratory survival analyses.
  
  
  CONCLUSIONS
  Discordances regarding HER2 status and ER status between CTCs and the primary tumor occurred frequently but had no prognostic impact in our MBC patient cohorts.
authors.affiliation: Erasmus MC Cancer Institute, Erasmus University Medical Center, Department of Medical Oncology and Cancer Genomics Netherlands, Wytemaweg 80, 3015 CN, Rotterdam, The Netherlands. Electronic address: n.beije@erasmusmc.nl.
authors.forename: Nick
authors.initials: N
authors.lastname: Beije
authors.affiliation: Erasmus MC Cancer Institute, Erasmus University Medical Center, Department of Medical Oncology and Cancer Genomics Netherlands, Wytemaweg 80, 3015 CN, Rotterdam, The Netherlands.
authors.forename: Wendy
authors.initials: W
authors.lastname: Onstenk
authors.affiliation: Erasmus MC Cancer Institute, Erasmus University Medical Center, Department of Medical Oncology and Cancer Genomics Netherlands, Wytemaweg 80, 3015 CN, Rotterdam, The Netherlands.
authors.forename: Jaco
authors.initials: J
authors.lastname: Kraan
authors.affiliation: Erasmus MC Cancer Institute, Erasmus University Medical Center, Department of Medical Oncology and Cancer Genomics Netherlands, Wytemaweg 80, 3015 CN, Rotterdam, The Netherlands.
authors.forename: Anieta M
authors.initials: AM
authors.lastname: Sieuwerts
authors.affiliation: Franciscus Gasthuis, Department of Internal Medicine, Kleiweg 500, 3045 PM, Rotterdam, The Netherlands.
authors.forename: Paul
authors.initials: P
authors.lastname: Hamberg
authors.affiliation: Oncology Center GZA Hospitals Sint Augustinus, Translational Cancer Research Unit, Department of Medical Oncology, Oosterveldlaan 26, 2610, Antwerp, Belgium.
authors.forename: Luc Y
authors.initials: LY
authors.lastname: Dirix
authors.affiliation: Oncology Center GZA Hospitals Sint Augustinus, Translational Cancer Research Unit, Department of Medical Oncology, Oosterveldlaan 26, 2610, Antwerp, Belgium.
authors.forename: Anja
authors.initials: A
authors.lastname: Brouwer
authors.affiliation: Ikazia Hospital, Department of Internal Medicine, Montessoriweg 1, 3083 AN, Rotterdam, The Netherlands.
authors.forename: Felix E
authors.initials: FE
authors.lastname: de Jongh
authors.affiliation: Erasmus MC Cancer Institute, Erasmus University Medical Center, Department of Medical Oncology and Cancer Genomics Netherlands, Wytemaweg 80, 3015 CN, Rotterdam, The Netherlands.
authors.forename: Agnes
authors.initials: A
authors.lastname: Jager
authors.affiliation: Erasmus MC Cancer Institute, Erasmus University Medical Center, Department of Medical Oncology and Cancer Genomics Netherlands, Wytemaweg 80, 3015 CN, Rotterdam, The Netherlands.
authors.forename: Caroline M
authors.initials: CM
authors.lastname: Seynaeve
authors.affiliation: Erasmus MC Cancer Institute, Erasmus University Medical Center, Department of Medical Oncology and Cancer Genomics Netherlands, Wytemaweg 80, 3015 CN, Rotterdam, The Netherlands.
authors.forename: Ngoc M
authors.initials: NM
authors.lastname: Van
authors.affiliation: Erasmus MC Cancer Institute, Erasmus University Medical Center, Department of Medical Oncology and Cancer Genomics Netherlands, Wytemaweg 80, 3015 CN, Rotterdam, The Netherlands.
authors.forename: John A
authors.initials: JA
authors.lastname: Foekens
authors.affiliation: Erasmus MC Cancer Institute, Erasmus University Medical Center, Department of Medical Oncology and Cancer Genomics Netherlands, Wytemaweg 80, 3015 CN, Rotterdam, The Netherlands.
authors.forename: John W M
authors.initials: JW
authors.lastname: Martens
authors.affiliation: Erasmus MC Cancer Institute, Erasmus University Medical Center, Department of Medical Oncology and Cancer Genomics Netherlands, Wytemaweg 80, 3015 CN, Rotterdam, The Netherlands.
authors.forename: Stefan
authors.initials: S
authors.lastname: Sleijfer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D005260:Female; D006801:Humans; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating / Q000378:metabolism*; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen