Does extirpation of the primary breast tumor give boost to growth of metastases? Evidence revealed by mathematical modeling.

A comprehensive mechanistic model of cancer natural history was utilized to obtain an explicit formula for the distribution of volumes of detectable metastases in a given secondary site at any time post-diagnosis. This model provided an excellent fit to the volumes of n=31, 20 and 15 bone metastases observed in three breast cancer patients 8 years, 5.5 years and 9 months after primary diagnosis, respectively. The model with optimal parameters allowed us to reconstruct the individual natural history of cancer for the first patient. This gave definitive answers, for the patient in question, to the following three questions of major importance in clinical oncology: (1) How early an event is metastatic dissemination of breast cancer? (2) How long is the metastasis latency time? and (3) Does extirpation of the primary breast tumor accelerate the growth of metastases? Specifically, according to the model applied to the first patient, (1) inception of the first metastasis occurred 29.5 years prior to the primary diagnosis; (2) the expected metastasis latency time was about 79.5 years; and (3) resection of the primary tumor was followed by a 32-fold increase in the rate of metastasis growth. The model and our conclusions were validated by the results for the two other patients.