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

  • Stella Mook
  • Marjanka K. Schmidt
  • Giuseppe Viale
  • Giancarlo Pruneri
  • Inge Eekhout
  • Arno Floore
  • Annuska M. Glas
  • Jan Bogaerts
  • Fatima Cardoso
  • Martine J. Piccart-Gebhart
  • Emiel T. Rutgers
  • Laura J. van’t Veer
  • 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

Authors and Affiliations

  • Stella Mook
    • 1
  • Marjanka K. Schmidt
    • 1
  • Giuseppe Viale
    • 2
    • 3
  • Giancarlo Pruneri
    • 2
    • 3
  • Inge Eekhout
    • 1
  • Arno Floore
    • 4
  • Annuska M. Glas
    • 4
  • Jan Bogaerts
    • 5
  • Fatima Cardoso
    • 6
  • Martine J. Piccart-Gebhart
    • 6
  • Emiel T. Rutgers
    • 7
  • Laura J. van’t Veer
    • 1
    • 4
  • On behalf of the TRANSBIG consortium
    • 8
  1. 1.Department of PathologyThe Netherlands Cancer InstituteAmsterdamThe Netherlands
  2. 2.Division of Pathology and Laboratory MedicineEuropean Institute of OncologyMilanItaly
  3. 3.School of MedicineUniversity of MilanMilanItaly
  4. 4.Agendia BVAmsterdamThe Netherlands
  5. 5.European Organisation for Research and Treatment of CancerBrusselsBelgium
  6. 6.Department of Medical OncologyJules Bordet InstituteBrusselsBelgium
  7. 7.Department of Surgical OncologyThe Netherlands Cancer InstituteAmsterdamThe Netherlands
  8. 8.