Breast cancer intratumor genetic heterogeneity: causes and implications.

There is burgeoning evidence to suggest that tumor evolution follows the laws of Darwinian evolution, whereby individual tumor cell clones harbor private genetic aberrations in addition to the founder mutations, and that these distinct populations of cancer cells interact in competitive and mutualistic manners. The combined effect of genetic and epigenetic instability, and differential selective pressures according to the microenvironment and therapeutic interventions, create many different evolutionary routes such that intratumor heterogeneity is inevitable. Numerous cytogenetic, comparative genomic hybridization and, more recently, massively parallel sequencing studies have generated indisputable evidence of this phenomenon. The impact of intratumor heterogeneity on response and resistance to therapy is beginning to be understood; this information may prove crucial for the potentials of personalized medicine to be realized. In this review, the evidence of intratumor heterogeneity in breast cancer, its potential causes and implications for the clinical management of breast cancer patients are discussed.