Estrogen, progesterone, and human epidermal growth factor receptor 2 discordance between primary and metastatic breast cancer

Breast Cancer Res Treat. 2020 Aug;183(1):137-144. doi: 10.1007/s10549-020-05746-8. Epub 2020 Jul 1.

Abstract

Background: The estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) statuses are frequently discordant between the primary tumor and metastatic lesions in metastatic breast cancer. This can have important therapeutic implications.

Patients and methods: In all, 541 patients with available receptor statuses from both primary tumor and metastatic lesion treated at Heidelberg and Tuebingen University Hospitals between 1982 and 2018 were included.

Results: Statistically significant discordance rates of 14% and 32% were found for ER and PR. HER2 status was statistically insignificantly discordant in 15% of patients. Gain in HER2 positivity was associated with an improved overall survival, whereas loss of HR positivity was associated with worse overall survival. Antiendocrine treatment differed in 20% of cases before and after biopsy and HER2-directed treatment in 14% of cases.

Conclusions: Receptor statuses are discordant between primary tumor and metastasis in a considerable fraction of patients with metastatic breast cancer. Next to a highly presumed predictive value with respect to efficacy of endocrine and HER2-targeted therapy, discordance seems to provide prognostically relevant information. Where feasible, metastatic lesions should be biopsied in accordance with current guidelines.

Keywords: Distant metastasis; Estrogen receptor (ER); Human epidermal growth factor receptor 2 (HER2); Metastatic breast cancer; Progesterone receptor (PR); Receptor status discordance.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Agents, Hormonal / therapeutic use
  • Biomarkers, Tumor
  • Breast Neoplasms / chemistry*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / pathology
  • Estrogens*
  • Female
  • Follow-Up Studies
  • Germany
  • Humans
  • Kaplan-Meier Estimate
  • Middle Aged
  • Molecular Targeted Therapy
  • Neoplasm Metastasis
  • Neoplasm Proteins / analysis*
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasms, Hormone-Dependent / chemistry*
  • Neoplasms, Hormone-Dependent / drug therapy
  • Neoplasms, Hormone-Dependent / pathology
  • Progesterone*
  • Protein Kinase Inhibitors / therapeutic use
  • Receptor, ErbB-2 / analysis*
  • Receptor, ErbB-2 / antagonists & inhibitors
  • Receptors, Estrogen / analysis*
  • Receptors, Progesterone / analysis*
  • Retrospective Studies
  • Young Adult

Substances

  • Antineoplastic Agents, Hormonal
  • Biomarkers, Tumor
  • Estrogens
  • Neoplasm Proteins
  • Protein Kinase Inhibitors
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Progesterone
  • ERBB2 protein, human
  • Receptor, ErbB-2