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Evaluating the investigational drug landscape for ESR1-mutated, estrogen receptor-positive, HER2-negative metastatic breast cancer
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DOI：10.1080/13543784.2026.2686701.png)
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Abstract
En 中文
Estrogen receptor-positive, HER2-negative (ER+/HER2−) metastatic breast cancer represents a major therapeutic challenge due to the frequent development of endocrine resistance. This review focuses on ESR1 mutations as key drivers of resistance and examines the evolving therapeutic strategies designed to overcome this mechanism.
The authors discuss current standards of care in the first- and second-line settings, with a focus on molecularly guided therapeutic strategies. The literature was identified through a targeted search of PubMed and ClinicalTrials.gov, focusing on English-language publications from peer-reviewed journals with additional reference to current ESMO and ASCO clinical practice guidelines. Particular attention was given to emerging oral ER-targeting agents. Key clinical trial data supporting ctDNA-based monitoring of ESR1 mutations and treatment adaptation were also reviewed.
Routine assessment of ESR1 mutations using liquid biopsy should be integrated into clinical practice to enable dynamic, molecularly guided treatment optimization. The expanding arsenal of ER-targeted therapies supports personalized sequencing strategies that move beyond rigid temporal cutoffs and improve outcomes in ET‑resistant disease.
Keywords:
Estrogen receptor alpha
breast neoplasms
ESR1 mutation
circulating tumor DNA
endocrine therapy resistance
hormone-receptor-positive breast cancer
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