title: Serum EGFR and serum HER-2/neu are useful predictive and prognostic markers in metastatic breast cancer patients treated with metronomic chemotherapy.
abstract: BACKGROUND
  Metronomic chemotherapy has been demonstrated to be of value in patients with advanced breast cancer. No reliable markers of response are available. In breast tumor, HER-2/neu is a prognostic factor, whereas no definite data exist for EGFR. The aim of the study was to evaluate the prognostic and predictive role of serum HER-2/neu and serum EGFR in breast cancer patients treated with low-dose chemotherapy.
  
  
  METHODS
  Serum levels of HER-2/neu (n = 135) and of EGFR (n = 113) were prospectively determined before the start of chemotherapy, after 2 months of treatment, and when progressive disease was diagnosed.
  
  
  RESULTS
  Elevated (>15 ng/mL) serum HER-2/neu before the start of chemotherapy was not associated with response rate, whereas elevated serum HER-2/neu at 2 months was significantly associated with reduced long-term clinical benefit (24 weeks) (P < .001), as well as changes in HER-2/neu levels between baseline and 2 months (P < .0001). Multivariate analysis identified a >or=20% increase of serum HER-2/neu as an independent factor for progression-free survival (PFS). Kinetics of serum HER-2/neu were significantly associated with PFS (P < .0001) and overall survival (OS) (P = .015). Low baseline serum levels of EGFR (<45 ng/mL) were predictive of reduced response rate both at 2 months (P = .031) and after 24 weeks (P = .022). Moreover, they were significantly associated with reduced PFS (P = .016) and OS (P = .015).
  
  
  CONCLUSIONS
  Serum HER-2/neu and EGFR may represent useful markers for early prediction of probability of response, PFS, and OS in patients with advanced breast cancer treated with metronomic chemotherapy.
authors.affiliation: Unit of Laboratory Medicine, European Institute of Oncology, Milan, Italy. maria.sandri@ieo.it
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Sandri
authors.forename: Harriet Ann
authors.initials: HA
authors.lastname: Johansson
authors.forename: Laura
authors.initials: L
authors.lastname: Zorzino
authors.forename: Michela
authors.initials: M
authors.lastname: Salvatici
authors.forename: Rita
authors.initials: R
authors.lastname: Passerini
authors.forename: Patrick
authors.initials: P
authors.lastname: Maisonneuve
authors.forename: Andrea
authors.initials: A
authors.lastname: Rocca
authors.forename: Giulia
authors.initials: G
authors.lastname: Peruzzotti
authors.forename: Marco
authors.initials: M
authors.lastname: Colleoni
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy*; D003520:Cyclophosphamide / Q000008:administration & dosage; D018450:Disease Progression; D018572:Disease-Free Survival; D004797:Enzyme-Linked Immunosorbent Assay; D066246:ErbB Receptors / Q000097:blood*; D005260:Female; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D011446:Prospective Studies; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000097:blood*; D013792:Thalidomide / Q000008:administration & dosage
chemical_list: D014408:Biomarkers, Tumor; D003520:Cyclophosphamide; D066246:ErbB Receptors; D008727:Methotrexate; D018719:Erb-b2 Receptor Tyrosine Kinases; D013792:Thalidomide