Defining the Biology of Estrogen Receptor-Low-Positive Breast Cancer

Background: We sought to better define estrogen receptor-low-positive (ER-low+) breast cancer biology and determine the utility of the Oncotype DX Breast Recurrence Score^® (RS) assay in this population. Methods: Patients with information regarding percentage ER positivity and PAM50 subtype were identified in The Cancer Genome Atlas (TCGA) and subtype distribution was determined. Next, patients with ER-low+ (ER 1–10%), HER2− breast cancer undergoing upfront surgery with known RS result were identified in the National Cancer Database (NCDB) and our institutional Dana-Farber Brigham Cancer Center (DF/BCC) database; RS distribution was examined. Finally, patients with ER-low+, HER2− breast cancer treated at DF/BCC from 2011 to 2020 without prior RS results and in whom tissue was available to perform the assay were identified. RS results, treatment, recurrence and breast cancer-specific survival (BCSS) were determined. Results: Of 1033 patients in TCGA, ER percentage and PAM50 subtype were available for 342 (33.1%) patients. Forty-six (13.5%) had ER-low+/HER2− tumors, among whom 82.6% were basal and 4.3% were luminal A. Among 3423 patients with ER-low+/HER2− disease in the NCDB, RS results were available for 689 (20.1%) patients; 67% had an RS ≥26. In our institutional database, only two patients with ER-low+/HER2− disease and an RS were identified, both with RS ≥26. Among 37 patients in our institutional cohort without prior RS, 35 (97.4%) had an RS ≥26, determined with testing. After a median follow-up of 40 months (range 3–106), three patients, all treated with chemotherapy, recurred. Three-year BCSS was 97.0% (95% confidence interval 96.9–97.1%). Conclusions: Most ER-low+/HER2− breast cancers are basal-like, with RS ≥26 suggesting these tumors are similar to triple-negative disease.