Spread of human cancer cells occurs with probabilities indicative of a nongenetic mechanism

There has been much uncertainty as to whether metastasis requires mutation at the time of spread. Here, we use clinical data to calculate the probability of the spread of melanoma and breast cancer cells. These calculations reveal that the probability of the spread of cancer cells is relatively high for small tumours (∼1 event of spread for every 500 cells for melanomas of 0.1 mm) and declines as tumours increase in size (∼1 event of spread for every 10(8) cells for melanomas of 12 mm). The probability of spread of breast cancer cells from the lymph nodes to the periphery is ∼1 event of spread for every 10(8) cells in the nodal masses, which have a mean diameter of 5 mm, while the probability of spread of cancer cells from the breast to the periphery when the primary masses are 5 mm is also ∼1 event of spread for every 10(8) cells. Thus, the occurrence of an event of spread from the breast to the lymph nodes appears not to increase the propensity of the progeny of those cells to spread from the lymph nodes to the periphery. These values indicate that the spread of human breast cancer and melanoma cells is unlikely to occur by a mechanism requiring mutation at the time of spread.