Conversion of epidermal growth factor receptor 2 and hormone receptor expression in breast cancer metastases to the brain

Breast Cancer Res. 2012 Aug 16;14(4):R119. doi: 10.1186/bcr3244.


Introduction: We investigated the status of estrogen receptor alpha (ERα), progesterone receptor (PR), and epidermal growth factor receptor 2 (HER2) in primary tumor and in the corresponding brain metastases in a consecutive series of breast cancer patients. Additionally, we studied factors potentially influencing conversion and evaluated its association with survival.

Methods: The study group included 120 breast cancer patients. ERα, PR, and HER2 status in primary tumors and in matched brain metastases was determined centrally by immunohistochemistry and/or fluorescence in situ hybridization.

Results: Using the Allred score of ≥ 3 as a threshold, conversion of ERα and PR in brain metastases occurred in 29% of cases for both receptors, mostly from positive to negative. Conversion of HER2 occurred in 14% of patients and was more balanced either way. Time to brain relapse and the use of chemotherapy or trastuzumab did not influence conversion, whereas endocrine therapy induced conversion of ERα (P = 0.021) and PR (P = 0.001), mainly towards their loss. Receptor conversion had no significant impact on survival.

Conclusions: Receptor conversion, particularly loss of hormone receptors, is a common event in brain metastases from breast cancer, and endocrine therapy may increase its incidence. Receptor conversion does not significantly affect survival.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / secondary*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology*
  • Breast Neoplasms / therapy
  • Combined Modality Therapy
  • Female
  • Follow-Up Studies
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Middle Aged
  • Neoplasm Grading
  • Receptor, ErbB-2 / genetics*
  • Receptor, ErbB-2 / metabolism
  • Receptors, Estrogen / genetics*
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / genetics*
  • Receptors, Progesterone / metabolism


  • Receptors, Estrogen
  • Receptors, Progesterone
  • Receptor, ErbB-2