1. Divisions of Diagnostic Oncology, Radiotherapy and Molecular Carcinogenesis and Center for Biomedical Genetics, The Netherlands Cancer Institute, 121 Plesmanlaan, 1066 CX Amsterdam, The Netherlands
2. Rosetta Inpharmatics, 12040 115th Avenue NE, Kirkland, Washington 98034, USA
3. These authors contributed equally to this work

Correspondence to: Stephen H. Friend³ Correspondence and requests for materials should be addressed to S.H.F. (e-mail: Email: stephen_friend@merck.com).

Breast cancer patients with the same stage of disease can have markedly different treatment responses and overall outcome. The strongest predictors for metastases (for example, lymph node status and histological grade) fail to classify accurately breast tumours according to their clinical behaviour^{1, 2, 3}. Chemotherapy or hormonal therapy reduces the risk of distant metastases by approximately one-third; however, 70–80% of patients receiving this treatment would have survived without it^{4, 5}. None of the signatures of breast cancer gene expression reported to date^{6, 7, 8, 9, 10, 11, 12} allow for patient-tailored therapy strategies. Here we used DNA microarray analysis on primary breast tumours of 117 young patients, and applied supervised classification to identify a gene expression signature strongly predictive of a short interval to distant metastases ('poor prognosis' signature) in patients without tumour cells in local lymph nodes at diagnosis (lymph node negative). In addition, we established a signature that identifies tumours of BRCA1 carriers. The poor prognosis signature consists of genes regulating cell cycle, invasion, metastasis and angiogenesis. This gene expression profile will outperform all currently used clinical parameters in predicting disease outcome. Our findings provide a strategy to select patients who would benefit from adjuvant therapy.