Clinical Behavior, Management, and Treatment Response of Estrogen Receptor Low (1–10%) Breast Cancer

Introduction Estrogen receptor (ER) and progesterone receptor (PR) guide management and impact outcomes of breast cancer (BC). This study compares ER-low (1–10%) with ER-negative (< 1%) and ER-positive (>10%) BC and investigates the significance of PR expression within ER-low disease. Patients and Methods All patients with HER2-negative invasive BC were identified from the National Cancer Database 2018–2019. Treatment and outcomes were compared using chi-squared tests and multivariable logistic regression. Results Of 232,762 patients, ER expression was: negative (13.8%), low (2.0%), and > 10% (84.2%). Chemotherapy was given in 83.9% of ER− disease, 82.4% of ER-low/PR− disease, 58.9% of ER-low/PR+ disease, and only in 22.9% of ER+ disease. Within the ER-low subgroup, adjuvant endocrine therapy, recurrence score, and Ki67 varied by PR status (all < 0.01). Patients with ER-low disease selected for neoadjuvant chemotherapy (NAC) were younger and had higher T and N category, tumor grade, and Ki67. With NAC, pathological complete response (pCR) rates were similar between ER-low/PR− and ER-low/PR+ (39.5% and 38.1%, respectively, p = 0.67), and were closer to the ER− group (39.7%) than the ER+ group (8.4%). On multivariable analysis, the adjusted effect of ER status (1–10% versus > 10%) on chemotherapy administration was odds ratio (OR) 8.2 (95% CI 7.3–9.2, p < 0.001) for PR-negative, and OR 3.3 (95% CI 7.3–9.2, p < 0.001) for PR-positive. Conclusions This study suggests that the tumor features and clinical management of ER-low tumors vary significantly by PR expression. Within ER-low tumors, PR− tumors more closely resemble ER− BC, while PR+ tumors exhibit less aggressive characteristics. In ER-low disease selected for treatment with NAC, response is similar to ER− regardless of PR status.