Breast cancer classification and prognosis based on gene expression profiles from a population-based study

August 13, 2003
100 (18) 10393-10398

Abstract

Comprehensive gene expression patterns generated from cDNA microarrays were correlated with detailed clinico-pathological characteristics and clinical outcome in an unselected group of 99 node-negative and node-positive breast cancer patients. Gene expression patterns were found to be strongly associated with estrogen receptor (ER) status and moderately associated with grade, but not associated with menopausal status, nodal status, or tumor size. Hierarchical cluster analysis segregated the tumors into two main groups based on their ER status, which correlated well with basal and luminal characteristics. Cox proportional hazards regression analysis identified 16 genes that were significantly associated with relapse-free survival at a stringent significance level of 0.001 to account for multiple comparisons. Of 231 genes previously reported by others [van't Veer, L. J., et al. (2002) Nature 415, 530-536] as being associated with survival, 93 probe elements overlapped with the set of 7,650 probe elements represented on the arrays used in this study. Hierarchical cluster analysis based on the set of 93 probe elements segregated our population into two distinct subgroups with different relapse-free survival (P < 0.03). The number of these 93 probe elements showing significant univariate association with relapse-free survival (P < 0.05) in the present study was 14, representing 11 unique genes. Genes involved in cell cycle, DNA replication, and chromosomal stability were consistently elevated in the various poor prognostic groups. In addition, glutathione S-transferase M3 emerged as an important survival marker in both studies. When taken together with other array studies, our results highlight the consistent biological and clinical associations with gene expression profiles.

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Acknowledgments

This work was supported in part by Fonds National de la Recherche Scientifique Grant Ext. 260 V6/5/2-ILF 14773 (to C.S.), the National Cancer Institute, and the Genome Institute of Singapore.

Supporting Information

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Information & Authors

Information

Published in

Go to Proceedings of the National Academy of Sciences
Go to Proceedings of the National Academy of Sciences
Proceedings of the National Academy of Sciences
Vol. 100 | No. 18
September 2, 2003
PubMed: 12917485

Classifications

Submission history

Received: December 13, 2002
Published online: August 13, 2003
Published in issue: September 2, 2003

Acknowledgments

This work was supported in part by Fonds National de la Recherche Scientifique Grant Ext. 260 V6/5/2-ILF 14773 (to C.S.), the National Cancer Institute, and the Genome Institute of Singapore.

Authors

Affiliations

Christos Sotiriou
Division of Clinical Sciences, National Cancer Institute, Advanced Technology Center, 8717 Grovemont Circle, Gaithersburg, MD 20877; Microarray Facility, Jules Bordet Institute, Free University of Brussels, 121 Boulevard de Waterloo, 1000 Brussels, Belgium; Genome Institute of Singapore, Singapore 117528; Biometric Research Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; and Imperial Cancer Research Fund Molecular Oncology Laboratory, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, OX3 9DS Oxford, United Kingdom
Soek-Ying Neo
Division of Clinical Sciences, National Cancer Institute, Advanced Technology Center, 8717 Grovemont Circle, Gaithersburg, MD 20877; Microarray Facility, Jules Bordet Institute, Free University of Brussels, 121 Boulevard de Waterloo, 1000 Brussels, Belgium; Genome Institute of Singapore, Singapore 117528; Biometric Research Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; and Imperial Cancer Research Fund Molecular Oncology Laboratory, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, OX3 9DS Oxford, United Kingdom
Lisa M. McShane
Division of Clinical Sciences, National Cancer Institute, Advanced Technology Center, 8717 Grovemont Circle, Gaithersburg, MD 20877; Microarray Facility, Jules Bordet Institute, Free University of Brussels, 121 Boulevard de Waterloo, 1000 Brussels, Belgium; Genome Institute of Singapore, Singapore 117528; Biometric Research Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; and Imperial Cancer Research Fund Molecular Oncology Laboratory, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, OX3 9DS Oxford, United Kingdom
Edward L. Korn
Division of Clinical Sciences, National Cancer Institute, Advanced Technology Center, 8717 Grovemont Circle, Gaithersburg, MD 20877; Microarray Facility, Jules Bordet Institute, Free University of Brussels, 121 Boulevard de Waterloo, 1000 Brussels, Belgium; Genome Institute of Singapore, Singapore 117528; Biometric Research Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; and Imperial Cancer Research Fund Molecular Oncology Laboratory, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, OX3 9DS Oxford, United Kingdom
Philip M. Long
Division of Clinical Sciences, National Cancer Institute, Advanced Technology Center, 8717 Grovemont Circle, Gaithersburg, MD 20877; Microarray Facility, Jules Bordet Institute, Free University of Brussels, 121 Boulevard de Waterloo, 1000 Brussels, Belgium; Genome Institute of Singapore, Singapore 117528; Biometric Research Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; and Imperial Cancer Research Fund Molecular Oncology Laboratory, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, OX3 9DS Oxford, United Kingdom
Amir Jazaeri
Division of Clinical Sciences, National Cancer Institute, Advanced Technology Center, 8717 Grovemont Circle, Gaithersburg, MD 20877; Microarray Facility, Jules Bordet Institute, Free University of Brussels, 121 Boulevard de Waterloo, 1000 Brussels, Belgium; Genome Institute of Singapore, Singapore 117528; Biometric Research Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; and Imperial Cancer Research Fund Molecular Oncology Laboratory, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, OX3 9DS Oxford, United Kingdom
Philippe Martiat
Division of Clinical Sciences, National Cancer Institute, Advanced Technology Center, 8717 Grovemont Circle, Gaithersburg, MD 20877; Microarray Facility, Jules Bordet Institute, Free University of Brussels, 121 Boulevard de Waterloo, 1000 Brussels, Belgium; Genome Institute of Singapore, Singapore 117528; Biometric Research Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; and Imperial Cancer Research Fund Molecular Oncology Laboratory, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, OX3 9DS Oxford, United Kingdom
Steve B. Fox
Division of Clinical Sciences, National Cancer Institute, Advanced Technology Center, 8717 Grovemont Circle, Gaithersburg, MD 20877; Microarray Facility, Jules Bordet Institute, Free University of Brussels, 121 Boulevard de Waterloo, 1000 Brussels, Belgium; Genome Institute of Singapore, Singapore 117528; Biometric Research Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; and Imperial Cancer Research Fund Molecular Oncology Laboratory, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, OX3 9DS Oxford, United Kingdom
Adrian L. Harris
Division of Clinical Sciences, National Cancer Institute, Advanced Technology Center, 8717 Grovemont Circle, Gaithersburg, MD 20877; Microarray Facility, Jules Bordet Institute, Free University of Brussels, 121 Boulevard de Waterloo, 1000 Brussels, Belgium; Genome Institute of Singapore, Singapore 117528; Biometric Research Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; and Imperial Cancer Research Fund Molecular Oncology Laboratory, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, OX3 9DS Oxford, United Kingdom
Edison T. Liu
Division of Clinical Sciences, National Cancer Institute, Advanced Technology Center, 8717 Grovemont Circle, Gaithersburg, MD 20877; Microarray Facility, Jules Bordet Institute, Free University of Brussels, 121 Boulevard de Waterloo, 1000 Brussels, Belgium; Genome Institute of Singapore, Singapore 117528; Biometric Research Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; and Imperial Cancer Research Fund Molecular Oncology Laboratory, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, OX3 9DS Oxford, United Kingdom

Notes

To whom correspondence should be addressed. E-mail: [email protected].
Communicated by Patrick O. Brown, Stanford University School of Medicine, Stanford, CA, May 14, 2003

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    Breast cancer classification and prognosis based on gene expression profiles from a population-based study
    Proceedings of the National Academy of Sciences
    • Vol. 100
    • No. 18
    • pp. 10137-10580

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