Estrogen receptor-low positive breast cancer: Historical perspective and recent advancements

The assessment of estrogen receptor (ER) expression in breast cancer, has traditionally been performed using ligand-binding assays, followed by immunohistochemistry, and is widely used to predict tumor response to endocrine therapy. ER-low positive breast cancer, formally defined in the 2020 ASCO/CAP testing guidelines, represents a small subset of invasive breast cancers characterized by 1 %-10 % of ER staining. Emerging evidence suggests that ER-low positive tumors constitute a heterogeneous group in terms of clinicopathologic features, molecular profiles, prognosis, and responsiveness to endocrine therapy. These tumors frequently behave more like ER-negative cancers, often displaying a more aggressive clinical course compared to classic ER-positive tumors. The clinical benefit of endocrine therapy in this subset remains uncertain, posing a significant challenge in determining the optimal treatment strategies. This review offers both a historical perspective and a comprehensive, up-to-date analysis of recent advancements in the understanding of ER-low positive breast cancer, with a focus on tumor biology, pathological evaluation, and clinical implications.