Breast cancer is the most frequently diagnosed nonskin cancer among women
in the United States and is second only to lung cancer in causing cancer-related
deaths among them (1). The vast majority of deaths are due to recurrent
metastatic disease. Occult dissemination of tumor cells is the main cause of
recurrent metastatic breast cancer (MBC) in patients who have undergone
resection of their primary tumor (2). Approximately 5% of patients with breast
cancer have clinically detectable metastases at the time of initial diagnosis, and
a further 30% to 40% of patients who appear clinically free of metastases
harbor occult metastases (3,4). The formation of metastatic colonies is a
continuous process, commencing early during the growth of the primary tumor.
Metastasis occurs through a cascade of linked sequential steps involving
multiple host-tumor interactions. This complex process requires the cells to
enter the circulation, arrest at the distant vascular bed, extravasate into the
organ interstitium and parenchyma, and proliferate as a secondary colony.
Several experimental studies suggest that during each stage of the process, only
the fittest tumor cells survive (2).