A paradox in breast cancer is that some of the same features that are associated with poor long term survival, such as high grade and ER negativity, are also associated with superior response to chemotherapy (high pCR rate) in the neoadjuvant setting; conversely, features associated with better long term survival, such as Luminal A classification and low grade, are associated with inferior chemo-sensitivity (low pCR rate) [39]. Here, ESR1 is linked to breast cancer.