The ligand‐independent reactivation of ER is the common driver of endocrine therapy resistance.[13] Therefore, the inhibition of ER itself or ER signaling pathway represent one of the most effective means to overcome resistance.[13] As a result, exploring novel strategies targeting key regulators in estrogen signaling pathway may provide effective ways to overcome endocrine therapy drug resistance and new sights for ER+ breast cancer therapy. Here, ESR1 is linked to breast carcinoma.