ArticleFrontiers in immunology2026
Distribution and molecular drivers of the 21-gene recurrence score in early breast cancer with low, intermediate, and high estrogen receptor expression.
Article in Frontiers in immunology, 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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Abstract
Background: Estrogen receptor (ER)-low human epidermal growth factor receptor 2 (HER2)-negative breast cancer shares similar pathological and molecular features with triple-negative breast cancer, yet the utility of the 21-gene assay in this population remains uncertain. This study aimed to evaluate the distribution and molecular drivers of the 21-gene recurrence score (RS) in early breast cancer with low, intermediate, and high ER expression. Methods: ER-positive, HER2-negative early breast cancer patients with 21-gene testing results from Shanghai Jiao Tong University Breast Cancer Database (2009-2022) were included. Eligible patients were categorized into three groups: ER-low (1-9%), ER-intermediate (10-50%), and ER-high (>50%). Chi-square and Kruskal-Wallis tests were conducted to compare the 21-gene RS and expression profiles among these groups. Spearman correlation and linear variance decomposition were performed to assess the associations between RS and its constituent gene modules. Results: A total of 4754 patients were included (ER‑low: 70, 1.5%; ER‑intermediate: 129, 2.7%; ER‑high: 4555, 95.8%). Mean RS values were 39, 32, and 24 in the three groups, with RS >25 observed in 72.9%, 62.8%, and 42.5% of patients, respectively (P < 0.001).. Among patients with ER-low tumors, the rates of RS >25 were 62.5% and 81.6% for those ≤50 or >50 years, 66.7% and 83.3% for those with low or high clinical risk, and 61.6% and 87.1% for those with PR-positive or PR-negative diseases, respectively. Notably, 90.6% younger patients had RS >15 in the ER-low group. Expression of Conclusions: The 21-gene RS was higher in ER-low breast cancer patients, particularly among those ≤50 years, with high clinical risk or PR-negative diseases. RS was only moderately correlated with proliferation features and minimally determined by any of the four module components in ER-low tumors. These findings are exploratory and require further validation in larger cohorts.
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