Neoplasia: An International Journal for Oncology Research (Nov 2016)

Prognostic Impact of HER2 and ER Status of Circulating Tumor Cells in Metastatic Breast Cancer Patients with a HER2-Negative Primary Tumor

  • Nick Beije,
  • Wendy Onstenk,
  • Jaco Kraan,
  • Anieta M. Sieuwerts,
  • Paul Hamberg,
  • Luc Y. Dirix,
  • Anja Brouwer,
  • Felix E. de Jongh,
  • Agnes Jager,
  • Caroline M. Seynaeve,
  • Ngoc M. Van,
  • John A. Foekens,
  • John W.M. Martens,
  • Stefan Sleijfer

Journal volume & issue
Vol. 18, no. 11
pp. 647 – 653


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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. CONCLUSION: 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.