Predictive and prognostic role of p53 according to tumor phenotype in breast cancer patients treated with preoperative chemotherapy: A single-institution analysis

Valentina Guarneri, Elena Barbieri, Federico Piacentini, Simona Giovannelli, Guido Ficarra, Antonio Frassoldati, Antonino Maiorana, Roberto D'Amico, PierFranco Conte

Research output: Contribution to journalArticle

Abstract

Introduction and aims: The p53 protein is a mediator of the cellular response to DNA damage. The aim of this study was to evaluate the predictive and/or prognostic value of p53 expression in relation to the molecular subtypes of breast cancer in patients treated with preoperative chemotherapy. Patients and methods: Patients with stage II-III breast cancer were included in the study. The expression of p53 was evaluated by immunohistochemistry on the diagnostic core biopsy specimen. Patients received 4-6 courses of preoperative chemotherapy. Pathological complete response (pCR) was defined as complete disappearance of invasive tumor in the breast and axillary lymph nodes. Results: 154 patients were included in the study and the molecular subtypes of their tumors were classified as follows: triple negative 18.2%, hormone receptor positive 60.4%, and HER2 positive 21.4%. p53 was expressed in 43.5% of the patients. A significant association between p53 expression and breast cancer molecular subtypes, tumor differentiation, and proliferation was observed. pCR was achieved in 8 patients (5.2%). p53 expression, molecular subtype, and nuclear grading were significant predictors of pCR (odds ratio for pCR in patients with p53-expressing tumors 10.03, p=0.0077). In univariate analysis, the expression of p53 as well as high proliferation and lymph node involvement after preoperative chemotherapy were predictors of a worse disease-free survival. Patients with p53 positivity also had a worse overall survival. In multivariate analysis, both p53 expression and nodal status after preoperative chemotherapy were significantly associated with disease-free and overall survival: the hazard ratios for relapse and death in patients with p53-expressing versus non-p53-expressing tumors were 2.29 (p=0.015) and 7.74 (p=0.002), respectively. The hazard ratios for relapse and death in node-positive versus node-negative patients were 3.63 (p=0.003) and 3.64 (p=0.041), respectively. Conclusions: In this series of patients, p53 expression was significantly associated with markers of aggressive tumor biology, and with a higher likelihood of attaining pCR. p53 expression was a negative prognostic parameter for disease-free and overall survival in univariate and multivariate analysis.

Original languageEnglish
Pages (from-to)104-111
Number of pages8
JournalInternational Journal of Biological Markers
Volume25
Issue number2
Publication statusPublished - 2010

Keywords

  • Breast cancer
  • Ki-67
  • Neoadjuvant chemotherapy
  • p53
  • Predictive factors
  • Primary systemic therapy
  • Prognostic factors
  • Tumor biomarkers

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cancer Research
  • Oncology
  • Pathology and Forensic Medicine
  • Medicine(all)

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