title: Prognostic and predictive impact of the HER-2/ neu extracellular domain (ECD) in the serum of patients treated with chemotherapy for metastatic breast cancer.
abstract: BACKGROUND
  The extracellular domain of the HER-2/neu -receptor (ECD) is shed from the receptor protein and can be detected in serum. However, the clinical implication of HER-2/neu ECD measurement must be further evaluated.
  
  
  METHODS
  In patients with metastatic breast cancer participating in a trial on first-line chemotherapy, the association of serum HER-2/neu ECD with progression-free interval, survival, and response was studied. Blood samples of patients receiving epirubicin and either cyclophosphamide (EC) or paclitaxel (ET) were collected before (n = 103) and in addition, after three courses of therapy (n = 46).
  
  
  RESULTS
  HER-2/neu ECD levels correlate with HER-2/neu overexpression of corresponding primary tumors determined by immunohistochemistry (antibody CB11, p = 0.018) with an optimized cut-off at 15 ng/mL. Elevated serum levels of HER-2/neu ECD before chemotherapy were correlated with shorter overall survival (p = 0.0097), but not with reduced progression-free survival and response to chemotherapy. In subgroup analyses, patients with elevated pretherapeutic HER-2/neu ECD levels treated with EC showed shorter overall survival (p = 0.0092); no difference was seen in the ET group. With regard to progression-free survival, patients with elevated HER-2/neu ECD levels tended to benefit from ET (p = 0.0341), in patients with low levels no difference was observed between EC and ET. A decrease of HER-2/neu ECD levels after three courses of therapy was associated with response to therapy (p = 0.006).
  
  
  CONCLUSIONS
  In our group of metastatic breast cancer patients, elevated HER-2/neu ECD levels are associated with decreased overall survival. With regard to progression-free survival, particularly patients with high HER-2/neu ECD levels seem to benefit from taxane-containing chemotherapy.
authors.affiliation: Department of Gynecology, University Hospital Hamburg-Eppendorf, Germany.
authors.forename: Volkmar
authors.initials: V
authors.lastname: Müller
authors.forename: Isabell
authors.initials: I
authors.lastname: Witzel
authors.forename: Hans Joachim
authors.initials: HJ
authors.lastname: Lück
authors.forename: Günter
authors.initials: G
authors.lastname: Köhler
authors.forename: Gunther
authors.initials: G
authors.lastname: von Minckwitz
authors.forename: Volker
authors.initials: V
authors.lastname: Möbus
authors.forename: Daniel
authors.initials: D
authors.lastname: Sattler
authors.forename: Waldemar
authors.initials: W
authors.lastname: Wilczak
authors.forename: Thomas
authors.initials: T
authors.lastname: Löning
authors.forename: Fritz
authors.initials: F
authors.lastname: Jänicke
authors.forename: Klaus
authors.initials: K
authors.lastname: Pantel
authors.forename: Christoph
authors.initials: C
authors.lastname: Thomssen
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D003520:Cyclophosphamide / Q000008:administration & dosage; D018450:Disease Progression; D018572:Disease-Free Survival; D004797:Enzyme-Linked Immunosorbent Assay; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017239:Paclitaxel / Q000008:administration & dosage; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis* / Q000097:blood*
chemical_list: D014408:Biomarkers, Tumor; D003520:Cyclophosphamide; D015251:Epirubicin; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases