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

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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.

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Acknowledgements

The authors would like to thank Hugo Horlings for providing immunohistochemistry data and Dimitry Nuyten for updating the clinical data for the Van de Vijver series and Michael Hauptman for helping with part of the statistical analyses. We are indebted to Sjoerd Rodenhuis, Rene Bernards, Marleen Kok and Philippe Bedard for critically reading the manuscript. This study was supported by the European Commission Framework Programme VI-TRANSBIG, the Dutch National Genomics Initiative-Cancer Genomics Center, and an unrestricted research grant from Agendia B.V.

Conflict of Interest

Laura J van’t Veer is a named inventor on a patent application for Mammaprint™ and reports holding equity in Agendia B.V. Arno Floore and Annuska M Glas are employees of Agendia B.V.

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Authors and Affiliations

  1. Department of Pathology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands

    Stella Mook, Marjanka K. Schmidt, Inge Eekhout & Laura J. van’t Veer

  2. Division of Pathology and Laboratory Medicine, European Institute of Oncology, Milan, Italy

    Giuseppe Viale & Giancarlo Pruneri

  3. School of Medicine, University of Milan, Milan, Italy

    Giuseppe Viale & Giancarlo Pruneri

  4. Agendia BV, Amsterdam, The Netherlands

    Arno Floore, Annuska M. Glas & Laura J. van’t Veer

  5. European Organisation for Research and Treatment of Cancer, Brussels, Belgium

    Jan Bogaerts

  6. Department of Medical Oncology, Jules Bordet Institute, Brussels, Belgium

    Fatima Cardoso & Martine J. Piccart-Gebhart

  7. Department of Surgical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands

    Emiel T. Rutgers

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  1. Stella Mook
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  2. Marjanka K. Schmidt
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  3. Giuseppe Viale
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  7. Annuska M. Glas
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  8. Jan Bogaerts
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  9. Fatima Cardoso
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  12. Laura J. van’t Veer
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On behalf of the TRANSBIG consortium

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Correspondence to Laura J. van’t Veer.

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Mook, S., Schmidt, M.K., Viale, G. et al. The 70-gene prognosis-signature predicts disease outcome in breast cancer patients with 1–3 positive lymph nodes in an independent validation study. Breast Cancer Res Treat 116, 295–302 (2009). https://doi.org/10.1007/s10549-008-0130-2

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  • DOI: https://doi.org/10.1007/s10549-008-0130-2

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