Breast cancer is the commonest malignancy in women. It is a heterogeneous disease with multiple sub-types, variable size, grade, metastatic potential and with varying prognosis. Among women with breast cancer in western countries, 30%-40% will develop metastatic disease.
Stephen Paget, using autopsy records of women with breast cancer demonstrated a non-random pattern of metastatic colonization. He hypothesised that tumor cells (the ‘seed’) have a specific affinity for the microenvironment of certain organs (the ‘soil’). In agreement with Paget’s ‘seed and soil hypothesis’, it has been shown in animal models that specific sets of genes can increase the potential of breast cancer cell lines to colonize distant specific sites, for instance bone and lung.
More than 90% of all cancer deaths are a direct consequence of the primary tumour successfully colonizing distant organs. The median survival from metastatic disease is approximately 20 months. In clinical practice, it is rare for patients to undergo a biopsy of metastatic disease. Although there is increasing recognition that metastatic deposits may have a different pattern of ER, PR and HER2 expression, biopsy of metastases, especially in deep-seated sites such as the brain is still rare. A further consequence of the trend not to biopsy metastases is that material is not readily available for research or to determine the best possible therapeutic options.
None-the-less, the development of new molecular methods including next generation sequencing is shedding light on breast cancer progression and metastases and highlighting aspects of heterogeneity amongst metastases initiating cells, the requirement for mutations that drive the metastatic process, the need for adaptation at distant sites and the organ specific phenotypes of the metastases.
These new data have implications for early detection as well as development of therapeutic options for metastatic disease.