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

Purpose: Estrogen receptor-positive (E[R.sup.+]) breast cancer (BC) is a heterogeneous disease, and there is an ongoing debate regarding the optimal cut point for clinically relevant ER expression. We used a real-world database to assess the prognostic and predictive values of lower ER expression levels on treatment outcomes with endocrine therapy. Methods: We used a nationwide electronic health record database. Descriptive statistics were used to evaluate the association between ER expression, tumor characteristics, and treatment patterns among patients with early-stage BC. We used Kaplan-Meier survival curves to estimate recurrence-free survival (RFS) and overall survival (OS). We assessed associations between an alternative ER expression-level cut point and clinical outcomes. Results: Among 4697 patients with early-stage HER2-negative BC, 83 (2.04%) had E[R.sup.+]-low BC (ER expression, 1-9.99%) and 36 (0.88%) had E[R.sup.+]-intermediate BC (10-19.9%). E[R.sup.+]-low tumors were associated with higher tumor grade, larger size, and higher axillary tumor burden than E[R.sup.+]-high tumors ([greater than or equal to]20% ER expression). African Americans had a higher prevalence of both triple-negative BC (TNBC) and E[R.sup.+]-low BC than E[R.sup.+]-high BC. Patients with E[R.sup.+]-low and E[R.sup.+]-intermediate tumors had survival outcomes similar to patients with TNBC and worse survival outcomes than patients with E[R.sup.+]-high tumors (P < 0.001). Tumors with