Systems Biology and Genomics of Breast Cancer

It is now accepted that breast cancer is not a single disease, but instead it is composed of a spectrum of tumor subtypes with distinct cellular origins, somatic changes, and etiologies. Gene expression profiling using DNA microarrays has contributed significantly to our understanding of the molecular heterogeneity of breast tumor formation, progression, and recurrence. For example, at least two clinical diagnostic assays exist (i.e., OncotypeDX RS and Mammaprint®) that are able to predict outcome in patients using patterns of gene expression and predetermined mathematical algorithms. In addition, a new molecular taxonomy based upon the inherent, or “intrinsic,” biology of breast tumors has been developed; this taxonomy is called the “intrinsic subtypes of breast cancer,” which now identifies five distinct tumor types and a normal breast-like group. Importantly, the intrinsic subtypes of breast cancer predict patient relapse, overall survival, and response to endocrine and chemotherapy regimens. Thus, most of the clinical behavior of a breast tumor is already written in its subtype profile. Here, we describe the discovery and basic biology of the intrinsic subtypes of breast cancer, and detail how this interacts with underlying genetic alternations, response to therapy, and the metastatic process.