206P - Prediction of disease outcome with quantitative measurement of HER-2 receptor expression and dimerization in patients with breast cancer

Date 30 September 2012
Event ESMO Congress 2012
Session Poster presentation II
Topics Biomarkers
Breast Cancer
Presenter Herve Bazin
Authors H. Bazin1, F. André2, M. Mathieu3, A. Ho-Pun-Cheung4, E. Lopez-Crapez4, G. Mathis5, P. Garnero1
  • 1Research, Cisbio Bioassays, 30200 - Codolet/FR
  • 2Department Of Medical Oncology, Institut Gustave Roussy, Villejuif/FR
  • 3Department Of Pathology, Institut Gustave Roussy, Villejuif/FR
  • 4Translational Research Unit, CRLC Val d’Aurelle Paul Lamarque,, Montpellier/FR
  • 5Research, Cisbio Bioassays, Codolet/FR

Abstract

Introduction

Expression of HER2 is commonly assessed by immunohistochemistry (IHC) and IHC-HER2 positive patients with breast cancer are candidate for anti-HER2 therapy. However IHC is not quantitative, does not allow to detect subtle changes in HER2 expression and cannot assess HER2 dimerization which is critical for its activation. The aim of this study was to quantify the expression and dimerization of HER2 in patients with breast cancer and to relate these measurements to disease outcome.

Methods

Using a novel microtiter plate based Time Resolved Fluorescence (TR-FRET) assay we quantify HER2 receptor expression and dimerization on frozen tumor samples from 100 patients with breast cancer. Normalized fluorescence signals allowed a quantitative measure of the overall receptors/dimers expression. Disease free (DFS) and overall survival (OS) was assessed in each subject.

Results

Among the 100 patients, 82 were IHC-HER2 negative, including 60 subjects who were ER+ and treated with hormonal therapy. Using Cox proportional hazard analyses we showed that in IHC-HER2 negative, ER+ subjects, the presence of HER2 dimer was significantly associated with both reduced DFS (p = 0.0001) and OS (p = 0.00237). Quantitative measure of HER2 expression was also associated with DFS (p = 0.0005) and OS (p = 0.03).

Conclusion

Quantitative measurement of expression and dimerization of HER2 by the novel TR-FRET assay predicts disease outcome in IHC-HER2 negative, ER+ breast cancer patients. These new biomarkers may be useful to identify failure patients to hormonal treatment who may benefit from adjuvant therapy with anti-HER therapy. Validation series is ongoing in 200 FFPE-samples and will be presented.

Disclosure

F. Andre: research funding.

M. Mathieu: research funding.

All other authors have declared no conflicts of interest.