Advances in the Molecular Taxonomy of Breast Cancer

Breast cancers are heterogeneous with variable morphologic features, biologic behavior and response to therapy. Traditional histopathologic features such as size, grade, and lymph node status may be used to provide a general estimate of outcome, stratifying patients into broad prognostic groups with prescribed guidelines for therapy. With this approach however, up to 85% of breast cancer patients are overtreated, and at the other end of the spectrum, 20% of patients succumb to their disease despite receiving maximum therapy. The current routine testing for the Estrogen receptor (ER) and HER2 growth factor receptor (HER2) represents the earliest attempts to provide a targeted approach to breast cancer therapy, based on molecular drivers of the disease. The pioneering works by Perou and Sorlie et al using global gene expression profiling introduced a molecular taxonomy of breast cancer with associated prognostic implications. The Luminal, HER2-enriched, and Basal-like intrinsic subtypes are generally characterized by the presence or absence of ER and HER2. They have been further analyzed and refined using integration of genomic and transcriptomic data made possible by advancements in high throughput molecular techniques and bioinformatics. Indeed, an increased understanding of the genomic landscape of these subtypes, and the molecular basis of breast cancer growth regulation, holds the promise of a more personalized patient selection for specific targeted therapies and improved outcomes.