Molecular classification of estrogen receptor-positive/luminal breast cancers

Estrogen receptor (ER)-positive breast cancer is the most prevalent subtype of invasive breast cancers. Patients with ER-positive breast cancers have variable clinical outcomes and responses to endocrine therapy and chemotherapy. With the advent of microarray-based gene expression profiling, unsupervised analysis methods have resulted in a classification of ER-positive disease into subtypes with different outcomes (ie, luminal A and luminal B); subsequent studies have demonstrated that these subtypes have different patterns of genetic aberrations and outcome. Studies based on supervised methods of microarray analysis have led to the development of prognostic gene signatures that identify a subgroup of ER-positive breast cancer patients with excellent outcome, who could forego chemotherapy. Despite the excitement with these approaches, several lines of evidence have demonstrated that the subclassification of ER-positive cancers and the prognostic value of gene signatures is largely driven by the expression levels of proliferation-related genes and that proliferation markers, such as Ki67, may provide equivalent prognostic information to that provided by gene signatures. In this review, we discuss the contribution of gene expression profiling to the classification of ER-positive breast cancer, the role of prognostic and predictive signatures, and the potential stratification of ER-positive disease according to their dependency on the phosphatidylinositol 3-kinase pathway.