title: Postoperative serum proteomic profiles may predict recurrence-free survival in high-risk primary breast cancer.
abstract: OBJECTIVE
  Better breast cancer prognostication may improve selection of patients for adjuvant therapy. We conducted a retrospective longitudinal study in which we investigated sera of high-risk primary breast cancer patients, to search for proteins predictive of recurrence-free survival.
  
  
  METHODS
  Sera of 82 breast cancer patients obtained after surgery, but prior to the administration of adjuvant therapy, were fractionated using anion-exchange chromatography, to facilitate the detection of the low-abundant serum peptides. Selected fractions were subsequently analysed by surface-enhanced laser desorption/ionisation time-of-flight mass spectrometry (SELDI-TOF MS), and the resulting protein profiles were searched for prognostic markers by appropriate bioinformatics tools.
  
  
  RESULTS
  Four peak clusters (i.e. m/z 3073, m/z 3274, m/z 4405 and m/z 7973) were found to bear significant prognostic value (P ≤ 0.01). The m/z 3274 candidate marker was structurally identified as inter-alpha-trypsin inhibitor heavy chain 4 fragment(658-688) in serum. Except for the m/z 7973 peak cluster, these peaks remained independently associated with recurrence-free survival upon multivariate Cox regression analysis, including clinical parameters of known prognostic value in this study population.
  
  
  CONCLUSIONS
  Investigation of the postoperative serum proteome by, e.g., anion-exchange fractionation followed by SELDI-TOF MS analysis is promising for the detection of novel prognostic factors. However, regarding the rather limited study population, validation of these results by analysis of independent study populations is warranted to assess the true clinical applicability of discovered prognostic markers. In addition, structural identification of the other markers will aid in elucidation of their role in breast cancer prognosis, as well as enable development of absolute quantitative assays.
authors.affiliation: Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute, Slotervaart Hospital, Amsterdam, The Netherlands. mcwgast@gmail.com
authors.forename: Marie-Christine W
authors.initials: MC
authors.lastname: Gast
authors.forename: Marc
authors.initials: M
authors.lastname: Zapatka
authors.forename: Harm
authors.initials: H
authors.lastname: van Tinteren
authors.forename: Marijke
authors.initials: M
authors.lastname: Bontenbal
authors.forename: Paul N
authors.initials: PN
authors.lastname: Span
authors.forename: Vivianne C G
authors.initials: VC
authors.lastname: Tjan-Heijnen
authors.forename: Jaco C
authors.initials: JC
authors.lastname: Knol
authors.forename: Connie R
authors.initials: CR
authors.lastname: Jimenez
authors.forename: Jan H M
authors.initials: JH
authors.lastname: Schellens
authors.forename: Jos H
authors.initials: JH
authors.lastname: Beijnen
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000097:blood / Q000401:mortality / Q000601:surgery*; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000097:blood*; D009364:Neoplasm Recurrence, Local; D016016:Proportional Hazards Models; D040901:Proteomics / Q000379:methods*; D015203:Reproducibility of Results; D012189:Retrospective Studies; D012306:Risk; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D009363:Neoplasm Proteins