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.

We analysed, with Affymetrix Human U133a GeneChips, the expression of 22 000 transcripts from total RNA of frozen tumour samples from 286 lymph-node-negative patients who had not received adjuvant systemic treatment.

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.

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.