The Clinical Utility of ESR1 Mutations in Hormone Receptor-Positive, HER2-Negative Advanced Breast Cancer

Abstract

The estrogen receptor is a key driver of estrogen receptor-positive breast cancers. Accumulating evidence indicates that the ESR1 ligand-binding domain mutations have an important role in acquired endocrine resistance, mainly to treatment with aromatase inhibitors. The identification, monitoring, and targeting of ESR1 mutations is an evolving field of major interest given the potential of improved outcomes in metastatic hormone receptor-positive breast cancers. Herein, the authors review the current evidence and rationale for exploiting the ESR1 mutations as a potential biomarker and therapeutic target. The authors discuss the role of ESR1 testing and current therapeutic efforts to target these mutations.

Keywords: Breast cancer; ESR1 mutation; Endocrine resistance; Endocrine treatment; Estrogen receptor; ctDNA.