The process of metastasis is a complex chain of events which is still incompletely understood. The metastatic potential of primary breast carcinomas is apparently influenced by genetic, environmental and cellular/molecular factors.

The first step is the dissemination of free, aggressive metastatic cells by the primary carcinoma. Most tumour cells with an epithelial morphology have a weak capability to metastasise: an epithelial-mesenchymal transition (EMT) generates aggressive cells that can detach from the primary tumour and disperse via the bloodstream, lymphatic system or body cavities, to invade the organ tissues and proliferate independently, finally establishing vascularised secondary tumours.

The metastatic phenotype has been thought to arise from random mutation, leading to cells with more aggressive characteristics including increased motility, high production of proteinases and angiogenic factors, and altered adhesion properties.

Recent research has however challenged the previous hypothesis that metastasis occurs as a result of random mutations of primary tumour cells. Researchers in the Netherlands identified a 70-gene profile that indicated poor prognosis in breast cancer with a lower probability of remaining free from distant metastases [1]. Results published by Ramaswamy in January 2003 found that a range of metastatic primary adenocarcinomas encode a 17 gene-expression signature found also in metastases [2].

In addition to these potential metastasis-promotor genes, six human metastasis-suppressor genes have been identified using in-vivo metastasis assays: NME1, KiSS1, KAI1, CAD1, BRMS1, and MKK4. This is a small number compared with the total number of tumour suppressor genes found. Restoring the function of these genes may block spread of metastases, possibly through regulation of EMT, although they are distinct from tumour suppressor genes and the resulting cells would still be tumorigenic. [3]

In fact, not all the genes found to date are functional for breast cancer, and the overall genetics of metastasis remains poorly understood. Advanced gene profiling and proteomics may provide a more accurate prognosis for breast cancer patients than, for example estrogen receptor diagnosis, so ensuring better survival rates for those affected by metastatic disease and the avoidance of adjuvant therapy where it is not required.

Gene profiling studies to date have shown promise but much more work is required, especially as studies have in general only analysed the overall survival rates rather than the observation of metastases developing in specific organs. Recent advances have been made, for instance identifying a road map to experimental bone metastases, but several issues need to be examined for a full understanding of the metastatic process both in bone and visceral organs, and for development of targeted therapeutics [4, 5]