117P - Anti-HER2 therapy efficacy in HER2-negative metastatic breast cancer with HER2-amplified circulating tumor cells: results of the CirCe T-DM1 trial

Date 11 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Anti-Cancer Agents & Biologic Therapy
Cancer in Adolescents
Breast Cancer, Metastatic
Breast Cancer
Translational Research
Presenter Francois-Clement Bidard
Citation Annals of Oncology (2017) 28 (suppl_5): v22-v42. 10.1093/annonc/mdx363
Authors F. Bidard1, P. cottu1, C. Dubot2, L. Venat-Bouvet3, A. Lortholary4, H. Bourgeois5, M. Bollet6, V. Servent Hanon7, E. Luporsi-Gely8, M. Espie9, S. Guiu10, V. D'Hondt11, V. Dieras1, M.P. Sablin1, S. Neffati1, F. Berger1, J. Pierga1, W. Jacot11
  • 1Medical Oncology, Institut Curie, 75005 - Paris/FR
  • 2Medical Oncology, Hôpital René Huguenin - Institut Curie, 92210 - St. Cloud/FR
  • 3Medical Oncology, limoges university hospital, 12000 - limoges/FR
  • 4Medical Oncology, Centre Catherine de Sienne, 44202 - Nantes/FR
  • 5Medical Oncology, Clinique Victor Hugo Le Mans, 72000 - Le Mans/FR
  • 6Radiation Oncology, Clinique Hartmann, 92300 - Levallois-Perret/FR
  • 7Medical Oncology, Centre Oscar Lambret, 59020 - Lille/FR
  • 8Medical Oncology, Institut de Cancérologie de Lorraine - Alexis Vautrin, 54519 - Vandoeuvre les Nancy/FR
  • 9Medical Oncology, Hôpital St. Louis, 75010 - Paris/FR
  • 10Medical Oncology, institut de cancerologie de montpellier, 34000 - montpellier/FR
  • 11Medical Oncology, ICM Regional Cancer Institute of Montpellier, 34298 - Montpellier/FR



Changes of HER2 status has been reported in circulating tumor cells (CTC) isolated from preclinical models and metastatic breast cancer (MBC) patients. The prospective multicentric phase II “CirCe T-DM1” trial was set up to assess whether HER2-amplified CTC are detectable in HER2-negative MBC and whether these cancers would respond to anti-HER2 therapy.


HER2-amplified CTC were screened in HER2-negative (HER2-/ER- and HER2-/ER+) MBC patients starting a 3rd line or 4th line of systemic therapy. CTC were detected by CellSearch® (Janssen Diagnostics) and FISH was performed on isolated CTCs. HER2-amplification was defined by a HER2/CEP17 ratio ≥2.2. Patients with ≥1 HER2-amplified CTC, measurable disease and adequate organ function were eligible. After stratification according to amplified CTC count (< vs ≥ 3), patients received single agent T-DM1. The primary endpoint of the study was the response rate by RECIST criteria.


From 11/2013 to 08/2016, 155 MBC patients were screened. 11 (9.2%) and 3 patients (2.5%) had 1-2 and ≥3 HER2-amplified CTCs respectively (minimal HER2/CEP17 ratio: 2.5). In the 14 patients with HER2-amplified CTC, the fraction of HER2-amplified CTCs among all detected CTCs was low (median 1.6%, range [0.3%-35.3%]), and presence of HER2-amplified CTCs was not associated with any patients’ characteristics. 11 patients were treated with single agent T-DM1. Partial response was confirmed in one patient with 1 HER2-amplified CTC (among 9 CTC detected); median PFS was 4.9 months (range: 1.8-10.1).


This study shows that CTCs with a true HER2-amplification can be detected in advanced HER2-negative MBC, mostly as a minor CTCs subset. Although one confirmed response was observed in our study, the overall low response rate to specific anti-HER2 therapy does not support the clinical utility of such strategy in that setting.

Clinical trial identification


Legal entity responsible for the study

Institut Curie




All authors have declared no conflicts of interest.