PURPOSE: Her-2/neu and p53-mediated signalling have been shown to interact at various cellular levels. However, the clinical relevance of p53 alterations in patients receiving trastuzumab for Her-2/neu-overexpressing metastatic breast cancer (MBC) remains unknown. The present study was performed to corroborate previous in vitro findings from our laboratory showing that trastuzumab induces growth arrest and apoptosis in a p53-independent manner. METHOD: Retrospective immunohistochemical (IHC) analysis for p53 protein expression was carried out on tumour specimens from 104 patients receiving trastuzumab-based treatment for Her-2/neu-overexpressing MBC at a single institution. p53 status was correlated with response (R) and clinical benefit (CB), median progression-free survival (PFS) time and overall survival (OAS) time in univariate and multivariate analyses. RESULTS: Characteristics were similar between p53-negative and p53-positive tumours (all P>0.05). In univariate analyses, R (39% vs 26%, P=0.208), CB (70% vs 57%, P=0.218), PFS (6.2 months vs 4.2 months, P=0.186) and OAS (23.8 months vs 23.2 months, P=0.650) were similar for p53-positive tumours and p53-negative tumours, respectively. In multivariate analyses, p53 status was not a significant predictor of R, CB, PFS or OAS (all P>0.05). CONCLUSIONS: p53 status, as determined by IHC, is not a predictor of the clinical efficacy of trastuzumab-based treatment in patients with Her-2/neu-overexpressing MBC.
PURPOSE:Her-2/neu and p53-mediated signalling have been shown to interact at various cellular levels. However, the clinical relevance of p53 alterations in patients receiving trastuzumab for Her-2/neu-overexpressing metastatic breast cancer (MBC) remains unknown. The present study was performed to corroborate previous in vitro findings from our laboratory showing that trastuzumab induces growth arrest and apoptosis in a p53-independent manner. METHOD: Retrospective immunohistochemical (IHC) analysis for p53 protein expression was carried out on tumour specimens from 104 patients receiving trastuzumab-based treatment for Her-2/neu-overexpressing MBC at a single institution. p53 status was correlated with response (R) and clinical benefit (CB), median progression-free survival (PFS) time and overall survival (OAS) time in univariate and multivariate analyses. RESULTS: Characteristics were similar between p53-negative and p53-positive tumours (all P>0.05). In univariate analyses, R (39% vs 26%, P=0.208), CB (70% vs 57%, P=0.218), PFS (6.2 months vs 4.2 months, P=0.186) and OAS (23.8 months vs 23.2 months, P=0.650) were similar for p53-positive tumours and p53-negative tumours, respectively. In multivariate analyses, p53 status was not a significant predictor of R, CB, PFS or OAS (all P>0.05). CONCLUSIONS:p53 status, as determined by IHC, is not a predictor of the clinical efficacy of trastuzumab-based treatment in patients with Her-2/neu-overexpressing MBC.
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Authors: Yoichi Nagata; Keng-Hsueh Lan; Xiaoyan Zhou; Ming Tan; Francisco J Esteva; Aysegul A Sahin; Kristine S Klos; Ping Li; Brett P Monia; Nina T Nguyen; Gabriel N Hortobagyi; Mien-Chie Hung; Dihua Yu Journal: Cancer Cell Date: 2004-08 Impact factor: 31.743
Authors: M D Pegram; A Lipton; D F Hayes; B L Weber; J M Baselga; D Tripathy; D Baly; S A Baughman; T Twaddell; J A Glaspy; D J Slamon Journal: J Clin Oncol Date: 1998-08 Impact factor: 44.544