title: Epidermal growth factor receptor status in breast cancer metastases to the central nervous system. Comparison with HER-2/neu status.
abstract: BACKGROUND
  The development of drug therapies (ZD1839) targeting epidermal growth factor receptor (EGFR) offers a pragmatic reason for exploring expression of EGFR in breast cancer, particularly metastatic breast cancer. There is a reported synergistic relationship between trastuzumab and ZD1839 therapy in patients with breast cancer. Although EGFR is the preferred dimerization partner for HER-2, it is unclear whether expression of these 2 interrelated receptors in a given patient with breast cancer would be parallel or mutually exclusive.
  
  
  OBJECTIVE
  To assess EGFR status in primary breast carcinoma versus metastatic central nervous system (CNS) sites and to compare results with HER-2/neu status in the same tumor.
  
  
  METHODS
  Central nervous system metastases (n = 51) from 33 patients and corresponding primary breast cancer specimens, when available (n = 11), were immunohistochemically stained for EGFR using a monoclonal mouse anti-EGFR antibody (clone 31G7) that recognizes both the wild-type form and the 145-kd variant III form of EGFR. The sections were evaluated by visual and image analysis techniques, and results were compared to previously assessed HER-2/neu status.
  
  
  RESULTS
  Epidermal growth factor receptor expression was found in CNS metastases from 39% of patients, with 82% concordance between the EGFR status of the primary breast and metastatic sites, and 92% concordance between the EGFR status among multiple CNS metastases in a given patient. Epidermal growth factor receptor and HER-2/neu status were concordant at the primary site in only 45% of patients. Additionally, EGFR and HER-2/neu status were concordant among multiple CNS metastases per individual case in only 45% of patients.
  
  
  CONCLUSIONS
  Thirty-nine percent of patients with metastatic breast cancer express EGFR, with parallel expression between metastatic sites and the primary neoplasm in 82% of the cases. The discordance in 18% of the cases, however, suggests that anti-EGFR agents might not show equal efficacy against metastatic tumor deposits and the primary tumor within a given patient. An additional corollary for pathologists based on this nonhomogeneity of receptor expression is that both the primary breast and multiple metastatic tumor deposits may need to be individually assessed for EGFR status. In our study, most metastatic tumor deposits showed expression for either EGFR or HER-2/neu, and less often for both, implying that drug therapies could be individualized for patients based on test results for both receptors.
authors.affiliation: Department of Pathology, University of Colorado Health Sciences Center, Denver 80262, USA.
authors.forename: Nichon L
authors.initials: NL
authors.lastname: Grupka
authors.forename: Kelly C
authors.initials: KC
authors.lastname: Lear-Kaul
authors.forename: Bette K
authors.initials: BK
authors.lastname: Kleinschmidt-DeMasters
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Singh
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000737:chemistry* / Q000473:pathology; D016543:Central Nervous System Neoplasms / Q000737:chemistry* / Q000556:secondary; D066246:ErbB Receptors / Q000032:analysis*; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D007150:Immunohistochemistry; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*
chemical_list: D066246:ErbB Receptors; D018719:Erb-b2 Receptor Tyrosine Kinases