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Validation of 70-gene prognosis signature in node-negative breast cancer

Breast Cancer Research and Treatment volume 117, pages 483–495 (2009)Cite this article

Abstract

Purpose The 70-gene prognosis signature (van’t Veer et al., Nature 415(6871):530–536, 2002) may improve the selection of lymph node-negative breast cancer patients for adjuvant systemic therapy. Optimal validation of prognostic classifiers is of great importance and we therefore wished to evaluate the prognostic value of the 70-gene prognosis signature in a series of relatively recently diagnosed lymph node negative breast cancer patients. Methods We evaluated the 70-gene prognosis signature in an independent representative series of patients with invasive breast cancer (N = 123; <55 years; pT1-2N0; diagnosed between 1996 and 1999; median follow-up 5.8 years) by classifying these patients as having a good or poor prognosis signature. In addition, we updated the follow-up of the node-negative patients of the previously published validation-series (Van de Vijver et al., N Engl J Med 347(25):1999–2009, 2002; N = 151; median follow-up 10.2 years). The prognostic value of the 70-gene prognosis signature was compared with that of four commonly used clinicopathological risk indexes. The endpoints were distant metastasis (as first event) free percentage (DMFP) and overall survival (OS). Results The 5-year OS was 82 ± 5% in poor (48%) and 97 ± 2% in good prognosis signature (52%) patients (HR 3.4; 95% CI 1.2–9.6; P = 0.021). The 5-years DMFP was 78 ± 6% in poor and 98 ± 2% in good prognosis signature patients (HR 5.7; 95% CI 1.6–20; P = 0.007). In the updated series (N = 151; 60% poor vs. 40% good), the 10-year OS was 51 ± 5% and 94 ± 3% (HR 10.7; 95% CI 3.9–30; P < 0.01), respectively. The DMFP was 50 ± 6% in poor and 86 ± 5% in good prognosis signature patients (HR 5.5; 95% CI 2.5–12; P < 0.01). In multivariate analysis, the prognosis signature was a strong independent prognostic factor in both series, outperforming the clinicopathological risk indexes. Conclusion The 70-gene prognosis signature is also an independent prognostic factor in node-negative breast cancer patients for women diagnosed in recent years.

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Acknowledgments

We are grateful to P.M. Ravdin (University of Texas, Health Science Centre, San Antonio (Texas), USA) for helpful advice with the use of Adjuvant! Online. In addition, we would like to thank G. Sonke for his help in the statistical analyses.

Competing interest statement

Dr. L.J. Van ‘t Veer, Dr. M.J. Van de Vijver and A.A.M. Hart are named inventors on a patent application for the 70-gene signature used in this study. Dr. Van’t Veer report being shareholder in and (part time) employed by Agendia, the commercial company that markets the 70-gene signature as MammaPrint®. A.N. Floore and A.M. Glas report being employed by Agendia.

Author information

Affiliations

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

    J. M. Bueno-de-Mesquita, J. Wesseling, R. de Groot, L. J. van’t Veer & M. J. van de Vijver

  2. Department of Medical Oncology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands

    S. C. Linn

  3. Department of Surgery, Reinier de Graaf Hospital, Reinier de Graafweg 3-11, 2625 AD, Delft, The Netherlands

    R. Keijzer & P. W. de Graaf

  4. Department of Radiotherapy, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands

    D. S. A. Nuyten & A. A. M. Hart

  5. Department of Pathology, Kennemer Gasthuis, PO Box 417, 2000 AK, Haarlem, The Netherlands

    C. van Krimpen

  6. Department of Pathology, VU Medical Center, PO Box 7057, 1007 MB, Amsterdam, The Netherlands

    C. Meijers

  7. Department of Internal Medicine, Reinier de Graaf Hospital, Reinier de Graafweg 3-11, 2625 AD, Delft, The Netherlands

    M. M. E. M. Bos

  8. Department of Surgical Oncology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands

    E. J. T. Rutgers

  9. Department of Experimental Therapy, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands

    H. Halfwerk

  10. Department of Pathology, Reinier de Graaf Hospital, Reinier de Graafweg 3-11, 2625 AD, Delft, The Netherlands

    A. Pronk

  11. Agendia BV, Kruislaan 406, 1098 SM, Amsterdam, The Netherlands

    A. N. Floore, A. M. Glas & L. J. van’t Veer

  12. Department of Pathology, Academic Medical Centre, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands

    M. J. van de Vijver

Authors
  1. J. M. Bueno-de-Mesquita
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  2. S. C. Linn
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  3. R. Keijzer
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  4. J. Wesseling
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  5. D. S. A. Nuyten
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  7. C. Meijers
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  8. P. W. de Graaf
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  9. M. M. E. M. Bos
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  10. A. A. M. Hart
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  11. E. J. T. Rutgers
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  12. J. L. Peterse
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  13. H. Halfwerk
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  14. R. de Groot
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  16. A. N. Floore
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  17. A. M. Glas
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  18. L. J. van’t Veer
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  19. M. J. van de Vijver
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Corresponding author

Correspondence to M. J. van de Vijver.

Additional information

J. L. Peterse—deceased.

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Bueno-de-Mesquita, J.M., Linn, S.C., Keijzer, R. et al. Validation of 70-gene prognosis signature in node-negative breast cancer. Breast Cancer Res Treat 117, 483–495 (2009). https://doi.org/10.1007/s10549-008-0191-2

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Keywords

  • Gene expression profile
  • Prognosis signature
  • Breast cancer
  • Microarray