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.
*Department of Pathology, Hospital Israelita Albert Einstein, Instituto Israelita de Ensino e Pesquisa, São Paulo, Brazil
†Molecular Pathology Laboratory, The Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research
‡Cancer Research UK London Research Institute, Lincoln’s Inn Fields, London, UK
D.N.R. and J.S.R-F. are funded by Breakthrough Breast Cancer. J.S.R-F. is a recipient of the 2010 CRUK Future Leaders Prize. B.W. is supported by a CRUK postdoctoral fellowship.
The authors have no conflicts of interest to disclose.
Reprints: Jorge S. Reis-Filho, MD, PhD, FRCPath, Molecular Pathology Laboratory, The Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK (e-mail: Jorge.Reis-Filho@icr.ac.uk).