p53 expression in node-positive breast cancer patients: Results from the Cancer and Leukemia Group B 9344 trial (159905) Journal Article


Authors: Lara, J. F.; Thor, A. D.; Dressler, L. G.; Broadwater, G.; Bleiweiss, I. J.; Edgerton, S.; Cowan, D.; Goldstein, L. J.; Martino, S.; Ingle, J. N.; Henderson, I. C.; Norton, L.; Winer, E. P.; Hudis, C. A.; Ellis, M. J.; Berry, D. A.; Hayes, D. F.
Article Title: p53 expression in node-positive breast cancer patients: Results from the Cancer and Leukemia Group B 9344 trial (159905)
Abstract: Purpose: 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]. Patients and 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. Conclusion: 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. ©2011 AACR.
Keywords: immunohistochemistry; adult; cancer survival; controlled study; protein expression; middle aged; major clinical study; overall survival; doxorubicin; paclitaxel; cancer staging; lymphatic metastasis; quality control; multiple cycle treatment; breast cancer; randomized controlled trial; cyclophosphamide; breast neoplasms; protein p53; monoclonal antibody; drug dose escalation; predictive value of tests; tumor suppressor protein p53; phase 3 clinical trial; cancer tissue; relapse free survival
Journal Title: Clinical Cancer Research
Volume: 17
Issue: 15
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2011-08-01
Start Page: 5170
End Page: 5178
Language: English
DOI: 10.1158/1078-0432.ccr-11-0484
PROVIDER: scopus
PMCID: PMC3149770
PUBMED: 21693655
DOI/URL:
Notes: --- - "Export Date: 3 October 2011" - "CODEN: CCREF" - "Source: Scopus"
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MSK Authors
  1. Clifford Hudis
    837 Hudis
  2. Larry Norton
    556 Norton