title: Tumor escape and progression of HER-2/neu negative breast cancer under immune pressure.
abstract: BACKGROUND
  Emerging data from pre-clinical and clinical studies suggest that HER-2/neu-specific T cell responses could induce HER-2/neu antigen loss in the tumor cells. These data suggest that patients with HER-2/neu negative breast cancer might have had HER-2/neu positive premalignant lesions in the past that progressed to HER-2/neu negative breast cancer under HER-2/neu-specific immune pressure.
  
  
  METHODS
  We conducted a pilot study in patients with HER-2/neu positive and HER-2/neu negative breast cancers as well as a patient with ductal carcinoma in situ (DCIS). HER-2/neu expression was determined by FISH. HER-2/neu-specific T cell responses were determined by using IFN-γ ELISA. Expression of IFN-γ Rα in the tumors was determined by immunohistochemistry analysis of paraffin-embedded tissues.
  
  
  RESULTS
  We determined that majority of (10 of 12) patients with HER-2/neu negative breast cancer had HER-2/neu-specific IFN-γ producing T cell responses which was stronger than those in patients with HER-2/neu positive tumors. Such immune responses were associated with nuclear translocation of IFN-γ Rα in their tumor cells. Patient with DCIS also showed HER-2/neu-specific T cell responses.
  
  
  CONCLUSIONS
  These data suggest that conducting retrospective studies in patients with HER-2/neu negative breast cancers and prospective studies in patients with HER-2/neu positive DCIS can determine whether HER-2/neu negative invasive carcinomas arise from HER-2/neu positive DCIS under the immune pressure.
authors: Department of Microbiology & Immunology, Virginia Commonwealth University Massey Cancer Center, Richmond, 23298, USA.
authors: Maciej
authors: M
authors: Kmieciak
authors: Kyle K
authors: KK
authors: Payne
authors: Michael O
authors: MO
authors: Idowu
authors: Margaret M
authors: MM
authors: Grimes
authors: Laura
authors: L
authors: Graham
authors: Maria-Libera
authors: ML
authors: Ascierto
authors: Ena
authors: E
authors: Wang
authors: Xiang-Yang
authors: XY
authors: Wang
authors: Harry D
authors: HD
authors: Bear
authors: Masoud H
authors: MH
authors: Manjili
mesh_terms: D001943:Breast Neoplasms / Q000276:immunology* / Q000473:pathology*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D021381:Protein Transport; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D017471:Receptors, Interferon / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D019139:Tumor Escape / Q000276:immunology*; D000096743:Interferon gamma Receptor
chemical_list: D007371:Interferon-gamma; D018719:Erb-b2 Receptor Tyrosine Kinases; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor; C508053:ERBB2 protein, human