A Gene-Expression Signature as a Predictor of Survival in Breast Cancer

N Engl J Med. 2002 Dec 19;347(25):1999-2009. doi: 10.1056/NEJMoa021967.

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.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Cohort Studies
  • Female
  • Gene Expression Profiling*
  • Humans
  • Lymphatic Metastasis
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Metastasis
  • Oligonucleotide Array Sequence Analysis
  • Patient Selection
  • Prognosis
  • Proportional Hazards Models
  • Survival Analysis