ESR1 and breast cancer: The OPTIMA (Optimal Personalised Treatment of early Breast Cancer using Multiparameter Analysis) trial25 opened in the UK in 2012 wherein patients with ER+/HER2−, pN1-2 or pN0 T > 30 mm are being randomized to standard therapy (chemotherapy and endocrine therapy) vs. test-directed therapy (chemotherapy for high risk patients only) with a goal to find the most cost-effective gene assay (RS compared to others) to define high risk women that benefit from chemotherapy for ER+/HER2− breast cancer.