1. ¹Division of Experimental Therapy, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands
2. ²Division of Diagnostic Oncology, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands
3. ³Information and Communication Theory Group, Delft University of Technology, 2600 GA Delft, The Netherlands
4. ⁴Division of Radiotherapy, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands
5. ⁵Rosetta Inpharmatics LLC, Seattle, WA 98109, USA

Correspondence: Dr LJ van't Veer, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands. E-mail: l.vt.veer@nki.nl

Received 9 April 2005; Revised 1 August 2005; Accepted 23 August 2005; Published online 27 September 2005.

Abstract

The axillary lymph node status is the most powerful prognostic factor for breast cancer patients to date. The molecular mechanisms that control lymph node metastasis, however, remain poorly understood. To define patterns of genes or gene regulatory pathways that drive breast cancer lymph node metastasis, we compared the gene expression profiles of 15 primary breast carcinomas and their matching lymph node metastases using microarrays. In general, primary breast carcinomas and lymph node metastases do not differ at the transcriptional level by a common subset of genes. No classifier or single gene discriminating the group of primary tumours from those of the lymph node metastases could be identified. Also, in a series of 295 breast tumours, no classifier predicting lymph node metastasis could be developed. However, subtle differences in the expression of genes involved in extracellular-matrix organisation and growth factor signalling are detected in individual pairs of matching primary and metastatic tumours. Surprisingly, however, different sets of these genes are either up- or downregulated in lymph node metastases. Our data suggest that breast carcinomas do not use a shared gene set to accomplish lymph node metastasis.