Population-based cohort study of treatment patterns and outcomes across ER expression subgroups in HER2-negative breast cancer

Estrogen receptor (ER) low (1-9%) breast cancer (BC) often behaves like triple-negative BC, while ERhigh (≥60%) disease has a more favorable prognosis. However, tumors with ER expressing 10-59% represent a poorly defined patient population. A nationwide cohort study in Sweden aimed to describe real-world patient characteristics, treatment patterns, and survival across the entire ER spectrum in HER2-negative BC. Tumors were stratified into five ER subgroups: ER 0% (ERzero), 1-9% (ERlow), 10-29% (ERmild), 30-59% (ERmod), and 60%-100% (ERhigh). The authors identified 75,211 patients diagnosed with HER2-negative BC in Sweden from 2007 to 2023. The figure shows the number of patients in each ER expression group and the unadjusted overall survival data. Compared to the ERhigh subgroup, both the ERmild (aHR 1.59; 95% CI 1.31-1.93) and the ERmod (1.31; 1.17-1.47) subgroups had significantly worse survival. Notably, ERmild patients had survival outcomes and molecular characteristics similar to those of ERlow and ERzero patients. Among patients with ERmild (aHR 0.46; 95% CI 0.23-0.94) and ERmod (0.60; 0.42-0.85) chemotherapy plus endocrine therapy was associated with lower risk of death compared with endocrine therapy alone. The authors conclude that these findings highlight the importance of assessment of ER-low, mild, and moderate tumors. Reporting ER as a percentage can provide additional biological insight in clinical decision making.