A new model for the dissemination of regional and distant metastases: implications for the sequencing of treatment of early breast cancer

After the primary breast tumor has reached a threshold volume V-0, metastasis is a time-dependent, compound Poisson process for each potential regional (e.g. axillary node) or distant (e.g, lung) site of spread. Therefore metastasis is considered to be random in time after the primary reaches V-0, but nonrandom with regard to the sites where metastases occur. Based on fits to data describing the incidence of metastases as a function of volume of primary breast cancer at the time of surgery, the predictions of the modelling are: (1) the rate of successful seeding per cubic centimeter of primary decreases rapidly as the primary grows, and (2) the estimated seeding frequency is sufficiently high that neoadjuvant treatment of early breast cancer should be reconsidered.