Molecular classification of breast cancer patients by gene expression profiling

For many tumuors, pathological subclasses exist which have to be further de fined by genetic markers to improve therapy and follow-up strategies. In th is study, cDNA array analyses of breast cancers have been performed to clas sify tumuors into categories based on expression patterns. Comparing purifi ed normal ductal epithelial cells and corresponding tumour tissues, the exp ression of only a small fraction of genes was found to be significantly cha nged. A subset of genes repeatedly found to be differentially expressed in breast cancers was subsequently employed to perform a classification of 82 normal and malignant breast specimens by cluster analysis. This analysis id entifies a subgroup of transcriptionally related tumours, designated class A, which can be further subdivided into A1 and A2. Correlation with classic al clinicopathological parameters revealed that subgroup A1 was characteriz ed by a high number of node-positive tumours (14 of 16). In this subgroup t here was a disproportionate number of patients who had already developed di stant metastases at the time of diagnosis (25%, in this subgroup, compared with 5%, among the rest of the samples). Taken together, the use of these d ifferentially expressed marker genes in conjunction with sample clustering algorithms provides a novel molecular classification of breast cancer speci mens, which facilitates the identification of patients with a higher risk o f recurrence. Copyright (C) 2001 John Wiley & Sons, Ltd.