Biological progression of breast cancer and clinical implications.

The classic view of tumor progression is that genetic mutation introduced in differentiated or progenitor cells causes tumors, through the acquisition of advantages for survival, and leading to phenotypic heterogeneity. Another theory (stem cell hypothesis) considers that tumor progression derives from cells within the tumor with stem cell characteristics of self-renewal and multiple differentiation potential. It is still unknown the timing of expression of various biological characteristics of breast cancer during the progression cascade, and the existence of clonal heterogeneity within primary tumor and synchronous or asynchronous distant metastases contributes to treatments failures.