title: p53 Expression in node-positive breast cancer patients: results from the Cancer and Leukemia Group B 9344 Trial (159905).
abstract: OBJECTIVE
  p53 as a prognostic and predictive factor in early-stage breast cancer has had mixed results. We studied p53 protein expression, by immunohistochemistry, in a randomized clinical trial of stage II patients treated with adjuvant doxorubicin and cyclophosphamide with or without paclitaxel [Cancer and Leukemia Group B (CALGB) 9344, INT0148].
  
  
  METHODS
  Epithelial p53 expression was evaluated using two immunohistochemical antibodies (DO7 and 1801) in formalin-fixed, paraffin-embedded tissue from patients with node-positive breast cancer who were randomized to four cycles of cyclophosphamide and one of three doses of doxorubicin (60, 75, or 90 mg/m(2); AC) and to receive four subsequent cycles of paclitaxel (T) or not. Prognostic and predictive value of p53 protein expression was assessed, independent of treatment assignment, for escalating doses of doxorubicin or addition of T with endpoints of relapse-free (RFS) and overall survival (OS).
  
  
  RESULTS
  Of 3,121 patients, 1,887 patient specimens treated on C9344 were obtained, passed quality control, and evaluated for p53 expression. Expression was 23% and 27% for mAbs 1801 and D07, respectively, with 92% concordance. In univariate analysis, p53 positivity was associated with worse OS with either antibody, but only p53 staining with monoclonal antibody 1801 had significantly worse RFS. In multivariate analysis, p53 was not predictive of RFS or OS from either doxorubicin dose escalation or addition of paclitaxel regardless of the antibody.
  
  
  CONCLUSIONS
  Nuclear staining of p53 by immunohistochemistry is associated with worse prognosis in node-positive patients treated with adjuvant doxorubicin-based chemotherapy but is not a useful predictor of benefit from doxorubicin dose escalation or the addition of paclitaxel.
authors.affiliation: Department of Pathology, Saint Barnabas Medical Center, Livingston, NJ 07039, USA. jlara@sbhcs.com
authors.forename: Jonathan F
authors.initials: JF
authors.lastname: Lara
authors.forename: Ann D
authors.initials: AD
authors.lastname: Thor
authors.forename: Lynn G
authors.initials: LG
authors.lastname: Dressler
authors.forename: Gloria
authors.initials: G
authors.lastname: Broadwater
authors.forename: Ira J
authors.initials: IJ
authors.lastname: Bleiweiss
authors.forename: Susan
authors.initials: S
authors.lastname: Edgerton
authors.forename: David
authors.initials: D
authors.lastname: Cowan
authors.forename: Lori J
authors.initials: LJ
authors.lastname: Goldstein
authors.forename: Silvana
authors.initials: S
authors.lastname: Martino
authors.forename: James N
authors.initials: JN
authors.lastname: Ingle
authors.forename: I Craig
authors.initials: IC
authors.lastname: Henderson
authors.forename: Larry
authors.initials: L
authors.lastname: Norton
authors.forename: Eric P
authors.initials: EP
authors.lastname: Winer
authors.forename: Clifford A
authors.initials: CA
authors.lastname: Hudis
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Ellis
authors.forename: Donald A
authors.initials: DA
authors.lastname: Berry
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Hayes
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008207:Lymphatic Metastasis; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage; D011237:Predictive Value of Tests; D011379:Prognosis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D016159:Tumor Suppressor Protein p53; D004317:Doxorubicin; D003520:Cyclophosphamide; D017239:Paclitaxel