Stage-related transcriptional changes in HR-positive/HER2-negative breast cancer

It is important to understand how the biology of breast cancer might differ with the burden of disease. Analyzing the expression of cancer-relevant genes with increasing diagnostic stage can provide insight into the changing biology of breast cancer and may also be clinically useful. Here, we evaluated the transcriptional activity according to stage of breast cancer (American Joint Committee on Cancer, AJCC Stage I to IV) from 1,152 patients with hormone receptor-positive HER2-negative breast cancer. Fresh tumor samples were prospectively collected for clinical-translational research with transcriptional profiling. Most transcriptional signatures remained consistent across stage categories, but the significant changes associated with increasing stage were attributed to endocrine escape, decreasing differentiation, increased complexity of signal transduction, and a few metabolic changes. The clinical relevance and implications of these findings are discussed. The expression data from these high-quality samples are a new publicly available resource for researchers.