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

Research output: Contribution to journalArticle

191 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)295-302
Number of pages8
JournalBreast Cancer Research and Treatment
Volume116
Issue number2
DOIs
Publication statusPublished - Jul 2009

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Validation Studies
Lymph Nodes
Breast Neoplasms
Genes
Neoplasm Metastasis
Neoplasms
Personal Autonomy
Survival
Adjuvant Chemotherapy
Transcriptome

Keywords

  • Gene expression signature
  • Node-positive breast cancer
  • Prognosis

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

The 70-gene prognosis-signature predicts disease outcome in breast cancer patients with 1-3 positive lymph nodes in an independent validation study. / Mook, Stella; Schmidt, Marjanka K.; Viale, Giuseppe; Pruneri, Giancarlo; Eekhout, Inge; Floore, Arno; Glas, Annuska M.; Bogaerts, Jan; Cardoso, Fatima; Piccart-Gebhart, Martine J.; Rutgers, Emiel T.; Van't Veer, Laura J.

In: Breast Cancer Research and Treatment, Vol. 116, No. 2, 07.2009, p. 295-302.

Research output: Contribution to journalArticle

Mook, S, Schmidt, MK, Viale, G, Pruneri, G, Eekhout, I, Floore, A, Glas, AM, Bogaerts, J, Cardoso, F, Piccart-Gebhart, MJ, Rutgers, ET & Van't Veer, LJ 2009, '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 Research and Treatment, vol. 116, no. 2, pp. 295-302. https://doi.org/10.1007/s10549-008-0130-2
Mook, Stella ; Schmidt, Marjanka K. ; Viale, Giuseppe ; Pruneri, Giancarlo ; Eekhout, Inge ; Floore, Arno ; Glas, Annuska M. ; Bogaerts, Jan ; Cardoso, Fatima ; Piccart-Gebhart, Martine J. ; Rutgers, Emiel T. ; Van't Veer, Laura J. / The 70-gene prognosis-signature predicts disease outcome in breast cancer patients with 1-3 positive lymph nodes in an independent validation study. In: Breast Cancer Research and Treatment. 2009 ; Vol. 116, No. 2. pp. 295-302.
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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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author = "Stella Mook and Schmidt, {Marjanka K.} and Giuseppe Viale and Giancarlo Pruneri and Inge Eekhout and Arno Floore and Glas, {Annuska M.} and Jan Bogaerts and Fatima Cardoso and Piccart-Gebhart, {Martine J.} and Rutgers, {Emiel T.} and {Van't Veer}, {Laura J.}",
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T1 - The 70-gene prognosis-signature predicts disease outcome in breast cancer patients with 1-3 positive lymph nodes in an independent validation study

AU - Mook, Stella

AU - Schmidt, Marjanka K.

AU - Viale, Giuseppe

AU - Pruneri, Giancarlo

AU - Eekhout, Inge

AU - Floore, Arno

AU - Glas, Annuska M.

AU - Bogaerts, Jan

AU - Cardoso, Fatima

AU - Piccart-Gebhart, Martine J.

AU - Rutgers, Emiel T.

AU - Van't Veer, Laura J.

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N2 - 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.

AB - 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.

KW - Gene expression signature

KW - Node-positive breast cancer

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