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Poster display

3179 - Effects of HER2 immuno-histochemistry expression levels on survival in patients treated by trastuzumab at the adjuvant setting in the SIGNAL/PHARE prospective cohort


10 Oct 2016


Poster display


Elsa Curtit


Annals of Oncology (2016) 27 (6): 43-67. 10.1093/annonc/mdw364


E. Curtit1, A. Vincent-Salomon2, S. Paget-Bailly1, G. Romieu3, P. Fumoleau4, H. Bonnefoi5, C. Jouannaud6, T. Petit7, A. Darut-Jouve8, V. Trillet-Lenoir9, C. Tarpin10, J. Pierga11, M. Rios12, J.P. Jacquin13, T. Bachelot14, D. Cox15, J. Deleuze16, I. Pauporte17, J. Henriques18, X. Pivot19

Author affiliations

  • 1 Oncology, CHU Besançon, Hôpital Jean Minjoz, 25000 - Besançon/FR
  • 2 Biopathology, Institut Curie, Paris/FR
  • 3 Oncology, ICM Regional Cancer Institute of Montpellier, Montpellier/FR
  • 4 Oncology, Centre Georges-François Leclerc (Dijon), Dijon/FR
  • 5 Oncology, Institute Bergonié, Bordeaux/FR
  • 6 Oncology, Institut Jean Godinot, Reims/FR
  • 7 Oncology, Centre Paul Strauss Centre de Lutte contre le Cancer, Strasbourg/FR
  • 8 -, Centre de Radiothérapie du Parc, Dijon/FR
  • 9 Oncology, Centre Hospitalier Lyon Sud, Lyon/FR
  • 10 Oncologie Médicale, Institute Paoli Calmettes, 13274 - Marseille/FR
  • 11 Medical Oncology, Institut Curie, 75248 - Paris/FR
  • 12 Oncology, Institut de Cancérologie de Lorraine - Alexis Vautrin, Vandoeuvre les Nancy/FR
  • 13 Oncology, Institut Lucien Neuwirth, saint priest en jarred/FR
  • 14 Service Oncologie Medicale, Centre Léon Bérard, Lyon/FR
  • 15 Scl - Inserm, Centre Léon Bérard, Lyon/FR
  • 16 Ceph, CEPH, Paris/FR
  • 17 Research, Institut National du Cancer, Boulogne-Billancourt/FR
  • 18 Biostatistic, CHU Besançon, Hôpital Jean Minjoz, Besançon/FR
  • 19 Service Oncologie Medicale, CHU Besançon, Hôpital Jean Minjoz, 25030 - Besançon/FR


Abstract 3179


The present study examines the possible impact related to the level of over-expression reported at +++ or ++ for HER2 on the magnitude of benefit achieved by adjuvant trastuzumab.


All patients with HER2-positive breast cancer, treated by trastuzumab and with available HER2 status by immuno-histochemistry (IHC) in the SIGNAL/PHARE prospective cohort were identified. Univariate and multivariate Cox proportional hazards models were performed to estimate associations between overall survival (OS) or disease free survival (DFS) and HER2 protein level of expression defined by +++ (IHC) or ++ (IHC) with a positive FISH. A propensity score and an inverse probability of treatment weighting (IPTW) approaches were performed to assess a possible variation of treatment effect according to HER2 status.


The SIGNAL/PHARE prospective cohort included 5474 patients with HER2-positive early breast cancer treated by trastuzumab. HER2 +++ was observed in 4942 cases and HER2 ++ with amplification assessed by FISH in 532 tumors. At baseline, patients with HER2 +++ tumors had higher incidence of inflammatory cancers, larger tumors and higher rate of hormone receptor-negative tumors. No significant association between HER2 expression in IHC and overall survival was detected, in multivariate analyses adjusted for prognostic factors (p = 0.17; HR = 1.33[0.89-1.99]). No association between HER2 expression and overall survival appeared through the propensity score and IPTW analysis (p = 0.33; HR = 1.09[0.92-1.28]). The same methods failed to demonstrate an association between HER2 level of expression and DFS (p > 0.05 and p > 0.05 respectively).


The level of expression of HER2 determined by IHC ( ++ with positive-FISH versus +++) did not impact OS and DFS of patients in HER2-positive early breast cancer treated by trastuzumab.

Clinical trial identification

NCT00381901 – RECF1098

Legal entity responsible for the study

INCa: Institut National du cancer (France)




All authors have declared no conflicts of interest.

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