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.