New insights into the pathogenesis of breast cancer metastasis

Synthesis and integration of macroscopic and microscopic findings on the pathogenesis of breast cancer and metastasis with recent cellular and molecular research on these topics provides a modern re-evaluation of the disease, which is relevant to clinical efforts and further research. At a microscopic level, tumors are not merely aggregates of malignant cells but are maladjusted living entities, which recruit host stromal cells such as fibroblasts, endothelial cells, etc. with which they intermingle and interact. The result is the formation of an expanding, distorted but recognizable caricature of the histology of the organ from which they are derived, which destroys adjacent normal tissue. The acquisition of metastatic capability endows the tumor with unique powers to parasitize other organs of the living host, with which it shares near complete genetic identity. This exceptional situation renders the parasitic cells almost invisible to host defences and poses a grave threat to host survival. The disseminated cancer cells present to the host defences very much the same problem that a guerilla army presents to orthodox military forces, because the disorderly tumor cells are difficult to distinguish from normal ones and are distributed in small units, in a large terrain. Recent evidence of disturbed molecular interactions between the colonizing and host populations offers the idea that one might be able to deploy classical counter-insurgency concepts based upon the dual approach, firstly of denying support from the indigenous population, by using drugs and secondly, of infiltrating the cells from within, using targeted genetic vectors. Both of these therapeutic approaches are not yet within our grasp, but we have recognized the nature of the adversary and will eventually be able to design tools to undermine its drive and progress.