Patient characteristics, treatment patterns, and survival across estrogen receptor expression subgroups in HER2-negative breast cancer: a population-based cohort study.

BACKGROUND: 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. In this nationwide cohort study, we aimed to describe real-world patient characteristics, treatment patterns and survival across the entire ER spectrum in Human Epidermal growth factor Receptor 2 (HER2)-negative BC. METHODS: We conducted a population-based cohort study of all women diagnosed with HER2-negative BC in Sweden (2007-2023), based on prospectively collected data. Tumors were stratified into five ER subgroups: ER0% (ERzero), ER1-9% (ERlow), ER10-29% (ERmild), ER30-59% (ERmod), and ER60-100% (ERhigh). We evaluated overall survival (OS) by ER subgroups and treatment (chemotherapy [CT] and endocrine therapy [ET]) using Kaplan-Meier analysis and multivariable Cox regression. FINDINGS: We included 75,211 patients. Compared to the ERhigh subgroup, both the ERmild (adjusted HR [aHR] = 1.59, 95% confidence interval [CI]: 1.31-1.93) and ERmod (aHR = 1.31, 95% CI: 1.17-1.47) subgroups had significantly worse survival (both adjusted P [aP] < 0.001). Notably, ERmild patients had survival outcomes and molecular characteristics similar to those of ERlow and ERzero patients. Patients with ERmild (aHR = 0.46, 95% CI: 0.23-0.94, aP = 0.033) and ERmod (aHR = 0.60, 95% CI: 0.42-0.85, aP = 0.0046) tumors, CT + ET was associated with a lower risk of death than ETonly. INTERPRETATION: Our findings highlight the importance of assessment of ER-low, mild and moderate tumors (1-59%). Reporting ER as a percentage can provide additional biological insight in clinical decision-making. FUNDING: This study received no external funding.