Abstract

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 22000 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.

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Gene-expression profiles to predict distant... [Lancet. 2005 Feb 19-25] - PubMed - NCBI

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