Our data suggest that ER+/PR- breast cancer represents a distinct disease subtype, which accounts for approximately 15% of breast cancers, shows fair reproducibility, and is associated with worse prognosis as compared with ER+/PR+ breast cancer; however, our genome-wide analysis identifies hundreds of genes that are significantly more prognostic than PR in ER+ breast cancer, suggesting that other candidate prognostic biomarkers are likely to outperform PR for predicting patient survival in ER+ breast cancer. The gene discussed is ESR1; the disease is breast cancer.