gms | German Medical Science

27th German Cancer Congress Berlin 2006

German Cancer Society (Frankfurt/M.)

22. - 26.03.2006, Berlin

Multi-center Validation of a Gene Expression Based Prognostic Signature in Lymph Node-Negative Primary Breast Cancer

Meeting Abstract

  • corresponding author presenting/speaker Manfred Schmitt - Frauenklinik, Technische Universität, München, Germany, Deutschland
  • J.A. Foekens - Department of Medical Oncology, Erasmus Medical Center – Daniel den Hoed Cancer Center, Rotterdam, The Netherlands
  • D. Atkins - Veridex LLC, San Diego, CA, USA
  • Y. Zhang - Veridex LLC, San Diego, CA, USA
  • F.C.G. Sweep - Department of Chemical Endocrinology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
  • N. Harbeck - Frauenklinik, Technische Universität, München, Germany
  • A. Paradiso - National Cancer Institute, Bari, Italy
  • T. Cufer - National Cancer Institute, Bari, Italy
  • J. Klijn - Department of Medical Oncology, Erasmus Medical Center – Daniel den Hoed Cancer Center, Rotterdam, The Netherlands
  • Y. Wang - Veridex LLC, San Diego, CA, USA

27. Deutscher Krebskongress. Berlin, 22.-26.03.2006. Düsseldorf, Köln: German Medical Science; 2006. DocPO036

The electronic version of this article is the complete one and can be found online at:

Published: March 20, 2006

© 2006 Schmitt et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.



Purpose: We previously identified in a single-center study a 76-gene prognostic signature for lymph node-negative (LNN) breast cancer patients (Wang et al., Lancet 2005, 365(9460):671). This study’s aim is to validate this gene signature in an independent more diverse population of LNN patients from multiple institutions.

Patients and Methods: Using custom-designed Affymetrix VDX2 GeneChips we analysed the expression of the 76 genes in RNA of frozen tumor samples from 180 LNN patients who did not receive adjuvant systemic treatment.

Results: In this independent validation, the 76-gene signature was highly informative in identifying patients with distant metastasis within 5 years (hazard ratio, HR, 7.41; 95% confidence interval CI, 2.63-20.9), even when corrected for traditional prognostic factors in multivariate analysis (HR, 11.36; 95% CI, 2.67-48.4). The actuarial 5 and 10-yr distant metastasis-free survival (DMFS) were 96% (95% CI, 89-99%) and 94% (95% CI, 83-98%), respectively for the good profile group and 74% (95% CI, 64-81%) and 65% (53-74%), respectively for the poor profile group. The sensitivity for 5-yr DMFS was 90%, the specificity 50%. The positive and negative predictive values were 35% (95% CI, 29-47%) and 94% (95% CI, 86-97%), respectively. The 76-gene signature was confirmed as a strong prognostic factor in subgroups of ER-positive patients, pre- and postmenopausal patients, and patients with tumor sizes ≤20 mm. The subgroup of patients with ER-negative tumors was considered too small to perform a separate analysis.

Conclusion: Our data provides a strong methodological and clinical multi-center validation of the pre-defined prognostic 76-gene signature in LNN breast cancer patients.