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

Ann Surg Oncol. 2023 Oct;30(11):6475-6483. doi: 10.1245/s10434-023-13846-0. Epub 2023 Jul 17.

Abstract

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.

MeSH terms

  • Biomarkers, Tumor
  • Breast Neoplasms* / pathology
  • Female
  • Humans
  • Ki-67 Antigen
  • Neoadjuvant Therapy
  • Receptor, ErbB-2 / metabolism
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism

Substances

  • Receptors, Estrogen
  • Ki-67 Antigen
  • Receptor, ErbB-2
  • Receptors, Progesterone
  • Biomarkers, Tumor