Breast Cancer Research and Treatment

, Volume 116, Issue 2, pp 295–302

The 70-gene prognosis-signature predicts disease outcome in breast cancer patients with 1–3 positive lymph nodes in an independent validation study

Authors

  • Stella Mook
    • Department of PathologyThe Netherlands Cancer Institute
  • Marjanka K. Schmidt
    • Department of PathologyThe Netherlands Cancer Institute
  • Giuseppe Viale
    • Division of Pathology and Laboratory MedicineEuropean Institute of Oncology
    • School of MedicineUniversity of Milan
  • Giancarlo Pruneri
    • Division of Pathology and Laboratory MedicineEuropean Institute of Oncology
    • School of MedicineUniversity of Milan
  • Inge Eekhout
    • Department of PathologyThe Netherlands Cancer Institute
  • Arno Floore
    • Agendia BV
  • Annuska M. Glas
    • Agendia BV
  • Jan Bogaerts
    • European Organisation for Research and Treatment of Cancer
  • Fatima Cardoso
    • Department of Medical OncologyJules Bordet Institute
  • Martine J. Piccart-Gebhart
    • Department of Medical OncologyJules Bordet Institute
  • Emiel T. Rutgers
    • Department of Surgical OncologyThe Netherlands Cancer Institute
    • Department of PathologyThe Netherlands Cancer Institute
    • Agendia BV
  • On behalf of the TRANSBIG consortium
Preclinical Study

DOI: 10.1007/s10549-008-0130-2

Cite this article as:
Mook, S., Schmidt, M.K., Viale, G. et al. Breast Cancer Res Treat (2009) 116: 295. doi:10.1007/s10549-008-0130-2

Abstract

Purpose The 70-gene prognosis-signature has shown to be a valid prognostic tool in node-negative breast cancer. Although axillary lymph node status is considered to be one of the most important prognostic factors, still 25–30% of node-positive breast cancer patients will remain free of distant metastases, even without adjuvant systemic therapy. We therefore investigated whether the 70-gene prognosis-signature can accurately identify patients with 1–3 positive lymph nodes who have an excellent disease outcome. Methods Frozen tumour samples from 241 patients with operable T1-3 breast cancer, and 1–3 positive axillary lymph nodes, with a median follow-up of 7.8 years, were selected from 2 institutes. Using a customized microarray, tumour samples were analysed for the 70-gene tumour expression signature. In addition, we reanalysed part of a previously described cohort (n = 106) with extended follow-up. Results The 10-year distant metastasis-free (DMFS) and breast cancer specific survival (BCSS) probabilities were 91% (SE 4%) and 96% (SE 2%), respectively for the good prognosis-signature group (99 patients), and 76% (SE 4%) and 76% (SE 4%), respectively for the poor prognosis-signature group (142 patients). The 70-gene signature was significantly superior to the traditional prognostic factors in predicting BCSS with a multivariate hazard ratio (HR) of 7.17 (95% CI 1.81 to 28.43; P  = 0.005). Conclusions The 70-gene prognosis-signature outperforms traditional prognostic factors in predicting disease outcome in patients with 1–3 positive nodes. Moreover, the signature can accurately identify patients with an excellent disease outcome in node-positive breast cancer, who may be safely spared adjuvant chemotherapy.

Keywords

Node-positive breast cancerGene expression signaturePrognosis

Supplementary material

10549_2008_130_MOESM1_ESM.pdf (151 kb)
(PDF 151 kb)

Copyright information

© Springer Science+Business Media, LLC. 2008