Estrogen receptor-low breast cancer:Biology chaos and treatment paradox

Hormone receptor testing mainly serves the purpose of guiding treatment choices for breast cancer patients.Patients with estrogen receptor(ER)-positive breast cancers show significant response to endocrine therapy.However,the methods to define ER status and eligibility for treatment remain controversial.Despite recent guidelines considering staining≥1% of tumor nuclei by immunohistology as ER-positive,it has raised concerns on the benefit of endocrine therapy for tumors with ER 1%-10% expression,termed“ER-low positive”.This subgroup accounts for 3% to 9% of all patients and is likely to have unique molecular features,and therefore distinct therapeutic response to endocrine therapy compared with ER-high positive tumors.The latest guidelines did not provide detailed descriptions for those patients,resulting in inconsistent treatment strategies.Consequently,we aimed to resolve this dilemma comprehensively.This review discusses molecular traits and recent ER-low positive breast cancer innovations,highlighting molecular-targeted treatment rather than traditional unified endocrine therapy for future basic and clinical research.