title: Molecular biomarkers for breast cancer prognosis: coexpression of c-erbB-2 and p53.
abstract: OBJECTIVE
  To assess the prognostic significance of molecular biomarkers, particularly c-erbB-2 and p53, through study of prospective clinical data and archival breast cancer tissues for women accrued to the Alabama Breast Cancer Project.
  
  
  BACKGROUND
  Defining molecular abnormalities in breast cancer is an important strategy for early detection, assessment of prognosis, and treatment selection. Evidence is strong that selective biomarkers, including c-erbB-2 and p53, have prognostic significance in breast cancer. Few studies have analyzed the prognostic significance of coexpression of biomarkers.
  
  
  METHODS
  Study patients were those accrued to the Alabama Breast Cancer Project (1975-1978) who had archival breast cancer tissues available for analysis. Criteria for entrance into the Alabama Breast Cancer Project were T1-3 breast cancer with M0 status. Age, nodal status, and histologic grade were also documented. Patients were randomized to radical versus modified radical mastectomy, and node-positive patients were also randomized to adjuvant chemotherapy (cyclophosphamide, methotrexate, and 5-fluorouracil [CMF]) versus melphalan. Archival breast cancer tissues were studied for c-erbB-2, TGF-alpha, p53, cathepsin D, bcl-2, and estrogen and progesterone receptor expression using immunohistochemistry. Survival curves were developed using the Kaplan-Meier method. Univariate analysis was performed using the log-rank test, multivariate analysis using a rank regression model.
  
  
  RESULTS
  Three hundred eleven patients were accrued to the Alabama Breast Cancer Project, and paraffin-embedded breast cancer tissues for 90 patients were available for immunohistochemical analysis of molecular biomarkers. Univariate analysis showed nodal status, c-erbB-2 expression, and p53 expression to have prognostic significance. Coexpression of c-erbB-2 and p53 was also found to have prognostic significance by the log-rank test. Multivariate analysis showed T stage, nodal status, c-erbB-2 expression, and p53 expression to have independent prognostic significance.
  
  
  CONCLUSIONS
  These data suggest that c-erbB-2 and p53 expression in breast cancer have prognostic significance. After median follow-up of 16 years, coexpression of c-erbB-2 and p53 may have more prognostic significance than traditional prognostic factors such as T stage and nodal status. Prospective study of large numbers of patients with breast cancer is encouraged to validate these findings.
authors.affiliation: Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama, USA. samuel.beenken@ccc.uab.edu
authors.forename: S W
authors.initials: SW
authors.lastname: Beenken
authors.forename: W E
authors.initials: WE
authors.lastname: Grizzle
authors.forename: D R
authors.initials: DR
authors.lastname: Crowe
authors.forename: M G
authors.initials: MG
authors.lastname: Conner
authors.forename: H L
authors.initials: HL
authors.lastname: Weiss
authors.forename: M T
authors.initials: MT
authors.lastname: Sellers
authors.forename: H
authors.initials: H
authors.lastname: Krontiras
authors.forename: M M
authors.initials: MM
authors.lastname: Urist
authors.forename: K I
authors.initials: KI
authors.lastname: Bland
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D015409:Mastectomy, Radical; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53