Gene expression profiling in breast cancer: towards individualising patient management

Breast cancer is a complex and clinically heterogeneous disease. The increase in knowledge of breast cancer biology has led to a number of clinical advances in the treatment of breast cancer, most notably the implementation of widespread mammography screening and advances in adjuvant treatment of early-stage disease. In the last 20 years, arrays of potential prognostic and/or predictive markers of breast cancer have been analysed. However, relatively few have proven to be clinically useful. To date, the only widely accepted markers for routine use in breast cancer are the oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor, HER-2 (c-erbB2/neu). Expression microarray technology and laser capture microdissection have now been employed to further our understanding of the molecular pathogenesis of breast cancer. Recently reported advances in array technology and RNA amplification methods are having a considerable impact in this field, allowing the analysis of pre-malignant and pre-invasive lesions. A number of studies have identified prognostic and predictive gene 'signatures', whose prediction of disease outcome and response to treatment is superior to conventional prognostic indicators. Despite major technological advances, a number of confounding issues remain concerning the potential clinical utility of gene expression profiling, including differences in study design, patient selection, array technology, chemistry, and methods of analysis. It seems likely, however, that following careful 'hypothesis driven' validation studies and clinical trials, expression profiling will be applied in the future to identify patient-specific disease profiles and provide rationale for individualised treatment. This review focuses on the current use and future potential of microarray profiling in breast cancer.