Gene-expression Profiles to Predict Distant Metastasis of Lymph-Node-Negative Primary Breast Cancer

Lancet. 2005 Feb 19-25;365(9460):671-9. doi: 10.1016/S0140-6736(05)17947-1.

Abstract

Background: Genome-wide measures of gene expression can identify patterns of gene activity that subclassify tumours and might provide a better means than is currently available for individual risk assessment in patients with lymph-node-negative breast cancer.

Methods: We analysed, with Affymetrix Human U133a GeneChips, the expression of 22000 transcripts from total RNA of frozen tumour samples from 286 lymph-node-negative patients who had not received adjuvant systemic treatment.

Findings: In a training set of 115 tumours, we identified a 76-gene signature consisting of 60 genes for patients positive for oestrogen receptors (ER) and 16 genes for ER-negative patients. This signature showed 93% sensitivity and 48% specificity in a subsequent independent testing set of 171 lymph-node-negative patients. The gene profile was highly informative in identifying patients who developed distant metastases within 5 years (hazard ratio 5.67 [95% CI 2.59-12.4]), even when corrected for traditional prognostic factors in multivariate analysis (5.55 [2.46-12.5]). The 76-gene profile also represented a strong prognostic factor for the development of metastasis in the subgroups of 84 premenopausal patients (9.60 [2.28-40.5]), 87 postmenopausal patients (4.04 [1.57-10.4]), and 79 patients with tumours of 10-20 mm (14.1 [3.34-59.2]), a group of patients for whom prediction of prognosis is especially difficult.

Interpretation: The identified signature provides a powerful tool for identification of patients at high risk of distant recurrence. The ability to identify patients who have a favourable prognosis could, after independent confirmation, allow clinicians to avoid adjuvant systemic therapy or to choose less aggressive therapeutic options.

MeSH terms

  • Adult
  • Aged
  • Breast Neoplasms / chemistry
  • Breast Neoplasms / classification
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Female
  • Gene Expression Profiling*
  • Humans
  • Lymphatic Metastasis
  • Middle Aged
  • Neoplasm Metastasis
  • Oligonucleotide Array Sequence Analysis*
  • Prognosis
  • ROC Curve
  • Receptors, Estrogen / analysis
  • Receptors, Progesterone / analysis
  • Sensitivity and Specificity

Substances

  • Receptors, Estrogen
  • Receptors, Progesterone