ArticleiScience2026
Dual cutoffs of estrogen receptor positivity define prognostic and predictive subgroups in breast cancer.
Article in iScience, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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6 authors.
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Abstract
Estrogen receptor (ER) expression informs treatment decisions in breast cancer, and the percentage of ER-positive cells may further influence clinical behavior. We analyzed four HER2-negative cohorts by integrating immunohistochemistry-based ER quantification with transcriptomic and immune profiling. The proportion of ER-positive cells was the strongest predictor of recurrence. Recurrence risk peaked around 45% ER positivity and decreased beyond this point, supporting 50% as a meaningful prognostic cutoff. Tumors with ER ≥ 50% demonstrated favorable survival, whereas ER <50% showed molecular features similar to triple-negative disease, including proliferative and metabolic pathway activation and p53/DNA repair signaling. Immune profiling identified immune depletion in ER-high tumors, B cell and macrophage enrichment in ER-low tumors, and strong immune activation in triple-negative tumors. In neoadjuvant chemotherapy cohorts, lower ER percentages were associated with greater chemosensitivity, and 14% distinguished response likelihood. These results indicate that continuous ER expression provides prognostic and therapeutic insight beyond current threshold-based classification.
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