Research advances on drug resistance mechanisms and therapeutic strategies for ESR1 gene alterations in breast cancer
WU Bingjun
ZHANG Jiabo
LU Lu
QI Yuanhang
CEN Lüjun
Abstract：Breast cancer is one of the most common malignancies in women.Endocrine therapy is a key strategy for estrogen receptor-positive breast cancer,yet resistance often leads to treatment failure.Alterations in the estrogen receptor 1(ESR1)gene represent a major mechanism of endocrine resistance,including point mutations,gene amplification,and gene fusions.Recent studies indicate that ligand-binding domain mutations confer resistance through estrogen-independent activation.The incidence and clinical relevance of ESR1 amplification remain controversial,while gene fusions constitute an emerging resistance mechanism.Novel agents targeting ESR1 mutations,such as oral selective estrogen receptor degraders and proteolysis-targeting chimeras,have shown promising efficacy in clinical trials.This review comprehensively outlines the roles of various ESR1 genomic alterations in resistance and recent therapeutic advances,offering new perspectives for overcoming resistance.
Keywords：breast cancerESR1 geneendocrine therapydrug resistancegene mutationgene amplificationgene fusion
Publication Date：2026-04-30
Online Publishing Date：2026-08-26(First online date of this platform, not the publication date of the document)
Pages：8( 608-614,619 )