ARTICLE

Metastasis, which is responsible for most cancer mortality, occurs through a multistep process, including invasion of tumor cells into the adjacent tissues, intravasation, survival in the circulation, extravasation from blood vessels, initiation and maintenance of micrometastases at distant sites, and finally, growth of cancer cells to produce secondary tumors ( 1 – 5). At each step, metastatic cancer cells face multiple obstacles that are overcome with molecular alterations that modify the expression and function of specific metastasis-related genes ( 1 – 3, 6, 7). Since 2000, the application of genomic profi ling methods to the analysis of human breast tumors has generated expression profi les that are predictive of metastasis ( 8 – 10). However, although such analyses are very powerful for identifying prognostic markers, it has been diffi cult to defi nitively attribute the development of metastasis to the specifi c contributions of these genes because o