Interestingly, the results of two of these trials provided initial evidence that: a) in the neoadjuvant setting, some patients with high-risk, early stage, hormone receptor-positive, HER2-negative, luminal B-positive, and breast cancer could achieve molecular down-staging of their disease with CDK4/6 inhibitor and endocrine therapy [521]; (b) in a neoadjuvant setting, the addition of the PI3K inhibitor taselisib to endocrine therapy increased the proportion of patients with ER+, HER2- early-stage breast cancer who achieved an objective response [312]. Here, ESR1 is linked to breast carcinoma.