The 21-gene recurrence score (RS) assay (Oncotype DxTM, Genomic Health, Redwood City, CA) is the most used prognostic assay in the United States, recommended by National Comprehensive Cancer Network and the American Society of Clinical Oncology for patients with early stage, estrogen receptor (ER)-positive, HER2-negative breast cancer [6]. The gene discussed is ESR1; the disease is breast cancer.