Recent data show that wide-spread use of target-matched strategies over the last 15 years have resulted in dramatic improvements in the prognosis of patients with estrogen-receptor (ER)-positive (Early Breast Cancer Trialists’ Collaborative Group 2005; Early Breast Cancer Trialists’ Collaborative Group 1998; Davies et al. 2011) and HER2-positive disease (Dawood et al. 2010; Yin et al. 2011; Harris et al. 2011), in both the early and advanced settings. This evidence concerns the gene ESR1 and breast cancer.