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Previous Volume 347:1999-2009 December 19, 2002 Number 25 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set Perspective by Sauter, G. Editorial by Kallioniemi, A. Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

ABSTRACT

Background A more accurate means of prognostication in breast cancer will improve the selection of patients for adjuvant systemic therapy.

Methods Using microarray analysis to evaluate our previously established 70-gene prognosis profile, we classified a series of 295 consecutive patients with primary breast carcinomas as having a gene-expression signature associated with either a poor prognosis or a good prognosis. All patients had stage I or II breast cancer and were younger than 53 years old; 151 had lymph-node–negative disease, and 144 had lymph-node–positive disease. We evaluated the predictive power of the prognosis profile using univariable and multivariable statistical analyses.

Results Among the 295 patients, 180 had a poor-prognosis signature and 115 had a good-prognosis signature, and the mean (±SE) overall 10-year survival rates were 54.6±4.4 percent and 94.5±2.6 percent, respectively. At 10 years, the probability of remaining free of distant metastases was 50.6±4.5 percent in the group with a poor-prognosis signature and 85.2±4.3 percent in the group with a good-prognosis signature. The estimated hazard ratio for distant metastases in the group with a poor-prognosis signature, as compared with the group with the good-prognosis signature, was 5.1 (95 percent confidence interval, 2.9 to 9.0; P<0.001). This ratio remained significant when the groups were analyzed according to lymph-node status. Multivariable Cox regression analysis showed that the prognosis profile was a strong independent factor in predicting disease outcome.

Conclusions The gene-expression profile we studied is a more powerful predictor of the outcome of disease in young patients with breast cancer than standard systems based on clinical and histologic criteria.

Source Information

From the Divisions of Diagnostic Oncology (M.J.V., L.J.V., D.W.V., J.L.P., D.A., A.W., A.G., L.D.), Radiotherapy (A.A.M.H., H.B.), Medical Oncology (S.R.), Biometrics (T.V.), Surgical Oncology (E.T.R.), and Molecular Carcinogenesis (R.B.), Netherlands Cancer Institute, Amsterdam; the Center for Biomedical Genetics, Amsterdam (R.B.); and Rosetta Inpharmatics, Kirkland, Wash. (Y.D.H., H.D., G.J.S., C.R., M.J.M., M.P., S.H.F.).

Drs. van de Vijver, He, and van 't Veer contributed equally to this article.

Address reprint requests to Dr. Bernards at the Division of Molecular Carcinogenesis, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands, or at r.bernards{at}nki.nl.

Full Text of this Article

Related Letters:

Gene-Expression Signatures in Breast Cancer
Helmbold P., Haerting J., Kölbl H., Kopans D. B., Kunkler I. H., Ransohoff D. F., van de Vijver M. J., He Y. D., van 't Veer L. J., Bernards R.
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N Engl J Med 2003; 348:1715-1717, Apr 24, 2003. Correspondence

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