A Real-World-Data Retrospective Cohort Study of Low Estrogen Receptor Positive Early Breast Cancer: Natural History and Treatment Outcomes.

Purpose Estrogen receptor–positive (ER+) breast cancer (BC) is a heterogeneous disease with an ongoing debate regarding the optimal cutoff point for clinically relevant ER expression. We used a real-world database to assess prognostic and predictive values of lower ER expression levels on treatment outcomes with endocrine therapy. Methods We used a nationwide electronic health record– (EHR-) derived deidentified database. Descriptive statistics were used to evaluate the correlation between ER expression, tumor characteristics, and treatment patterns among patients with early-stage BC. We used Kaplan-Meier survival curves to estimate relapse-free survival (RFS) and overall survival (OS). To assess an optimal ER expression level cut point, correlations between ER+ expression and clinical outcomes were performed. Results Among 4697 patients with early-stage BC, 83 (1.76%) had ER+-low BC (ER expression, 1%-9.99%), and 36 (0.8%) had ER+-intermediate BC (10%-19.9%). ER+-low tumors were associated with higher tumor grade, larger size and higher axillary tumor burden than ER+-high tumors (≥ 20% ER expression). African Americans had a higher prevalence of both triple-negative BC (TNBC; 21%) and ER+-low BC (22%) than ER+-high tumors (8%). Patients with ER+-low and ER+-intermediate tumors had survival outcomes similar to patients with TNBC and worse survival outcomes than patients with ER+-high tumors (P < .001). No significant correlations between endocrine therapy and RFS or OS were observed among patients with either ER+-low or ER+-intermediate BCs. Further tumors with < 20% ER expression were associated with worse outcomes. Conclusions Patients with ER expression levels < 20% derive minimal benefit from endocrine therapies.