Breast cancer patients with the same stage of disease can have markedly different treatment responses and overall outcome. The strongest predictors for metastasis (i.e. lymph node status and histological grade) fail to optimally classify breast tumors according to their clinical behavior.

Chemotherapy and/or hormonal therapy reduce the risk of distant metastases by approximately one-third; however, 70-80% of patients receiving this treatment would have survived without it. A more accurate means of prognostication is needed to improve the selection of patients for adjuvant systemic therapy.

By performing DNA microarray analysis on primary breast tumors of patients, Agendia were able to identify a gene expression signature that was strongly prognostic for development of distant metastasis in lymph node negative patients. The 70-gene prognosis expression signature consists of genes regulating cell cycle, invasion, metastasis and angiogenesis.

The gene expression profile was validated on a consecutive set of over 1000 patients (mainly European) and has been demonstrated to outperform all currently used clinical parameters in predicting disease outcome.

Comparison of survival analysis carried out using gene expression profiling compared to the St. Gallen criteria:

High risk patients identified by MammaPrint^® gene expression profiling have a higher rate of distant metastases than the high risk patients identified by the St. Gallen criteria.

Low risk patients identified by gene expression profiling have a higher likelihood of metastasis-free survival than those classified using the St. Gallen criteria.

Studies show that gene expression profiling identified 40% of all patients as low risk (good prognosis), compared to only 15% when risk is determined by the St. Gallen criteria.

Publications
Laura van 't Veer et al., Gene expression profiling predicts clinical outcome of breast cancer, Nature, vol 415, 31 January 2002, 530 - 535.

Marc van de Vijver et al., A gene expression signature as a predictor of survival in breast cancer, New England Journal of Medicine, vol 347, no 25, 19 December 2002, 1999-2009.

Marc Buyse et al., Validation and clinical utility of a 70-gene prognostic signature for women with a node-negative breast cancer, Journal of the National Cancer Institute, vol 98, no 17, 6 September 2006, 1183-1192.

Annuska Glas et al., Converting a breast cancer microarray signature into a high-throughput diagnostic test, BioMed Central Genomics 2006, vol 278, no 7, 30 October 2006, 2164-2167.