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PTEN activation contributes to tumor inhibition by trastuzumab, and loss of PTEN predicts trastuzumab resistance in patients.PTEN激活有助于曲妥珠单抗抑制肿瘤，而PTEN缺失预示着患者对曲妥珠单抗耐药。
Cancer Cell. 2004 Aug;6(2):117-27. doi: 10.1016/j.ccr.2004.06.022.
2
The efficacy of Herceptin therapies is influenced by the expression of other erbB receptors, their ligands and the activation of downstream signalling proteins.赫赛汀疗法的疗效受其他erbB受体的表达、其配体以及下游信号蛋白激活的影响。
Br J Cancer. 2004 Sep 13;91(6):1190-4. doi: 10.1038/sj.bjc.6602090.
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The PIK3CA gene is mutated with high frequency in human breast cancers.PIK3CA基因在人类乳腺癌中高频突变。
Cancer Biol Ther. 2004 Aug;3(8):772-5. doi: 10.4161/cbt.3.8.994. Epub 2004 Aug 26.
4
Phosphorylation/cytoplasmic localization of p21Cip1/WAF1 is associated with HER2/neu overexpression and provides a novel combination predictor for poor prognosis in breast cancer patients.p21Cip1/WAF1的磷酸化/细胞质定位与HER2/neu过表达相关，并为乳腺癌患者预后不良提供了一种新的联合预测指标。
Clin Cancer Res. 2004 Jun 1;10(11):3815-24. doi: 10.1158/1078-0432.CCR-03-0527.
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The hierarchical relationship between MAPK signaling and ROS generation in human leukemia cells undergoing apoptosis in response to the proteasome inhibitor Bortezomib.在响应蛋白酶体抑制剂硼替佐米而发生凋亡的人白血病细胞中，MAPK信号传导与活性氧生成之间的层级关系。
Exp Cell Res. 2004 May 1;295(2):555-66. doi: 10.1016/j.yexcr.2004.02.001.
6
Spectrum of p53 tumor suppressor gene mutations and breast cancer survival.p53肿瘤抑制基因突变谱与乳腺癌生存率
Breast Cancer Res Treat. 2004 Jan;83(1):57-66. doi: 10.1023/B:BREA.0000010699.53742.60.
7
The role of HER2/neu expression and trastuzumab in non-small cell lung cancer.HER2/neu 表达及曲妥珠单抗在非小细胞肺癌中的作用
Semin Oncol. 2004 Feb;31(1 Suppl 1):75-82. doi: 10.1053/j.seminoncol.2003.12.018.
8
The combination of p53 mutation and neu/erbB-2 amplification is associated with poor survival in node-negative breast cancer.p53 突变与 neu/erbB - 2 扩增相结合，与淋巴结阴性乳腺癌患者的不良生存情况相关。
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Control of apoptosis by p53.p53对细胞凋亡的调控
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Molecular mechanisms underlying IGF-I-induced attenuation of the growth-inhibitory activity of trastuzumab (Herceptin) on SKBR3 breast cancer cells.IGF-I诱导曲妥珠单抗（赫赛汀）对SKBR3乳腺癌细胞生长抑制活性减弱的分子机制。
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曲妥珠单抗在人表皮生长因子受体2（Her-2/neu）过表达的转移性乳腺癌中的疗效与p53状态无关。

The efficacy of trastuzumab in Her-2/neu-overexpressing metastatic breast cancer is independent of p53 status.

作者信息

Köstler Wolfgang J, Brodowicz Thomas, Hudelist Gernot, Rudas Margaretha, Horvat Reinhard, Steger Günther G, Singer Christian F, Attems Johannes, Rabitsch Werner, Fakhrai Negar, Elandt Katarzyna, Wiltschke Christoph, Hejna Michael, Zielinski Christoph C

机构信息

Clinical Division of Oncology, Department of Medicine I, Medical University of Vienna, 18-20 Waehringer Guertel, 1090, Vienna, Austria.

出版信息

J Cancer Res Clin Oncol. 2005 Jul;131(7):420-8. doi: 10.1007/s00432-005-0670-3. Epub 2005 Apr 29.

DOI:10.1007/s00432-005-0670-3
PMID:15864644
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12161263/
Abstract

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.

摘要

目的

已证实在多个细胞水平上，Her-2/neu和p53介导的信号传导存在相互作用。然而，对于接受曲妥珠单抗治疗的Her-2/neu过表达转移性乳腺癌（MBC）患者，p53改变的临床相关性仍不清楚。本研究旨在证实我们实验室先前的体外研究结果，即曲妥珠单抗以p53非依赖的方式诱导生长停滞和凋亡。

方法

对一家机构中104例接受基于曲妥珠单抗治疗的Her-2/neu过表达MBC患者的肿瘤标本进行p53蛋白表达的回顾性免疫组织化学（IHC）分析。在单因素和多因素分析中，将p53状态与缓解率（R）、临床获益（CB）、中位无进展生存期（PFS）和总生存期（OAS）进行相关性分析。

结果

p53阴性和p53阳性肿瘤的特征相似（所有P>0.05）。在单因素分析中，p53阳性肿瘤和p53阴性肿瘤的R（39%对26%，P=0.208）、CB（70%对57%，P=0.218）、PFS（6.2个月对4.2个月，P=0.186）和OAS（23.8个月对23.2个月，P=0.650）分别相似。在多因素分析中，p53状态不是R、CB、PFS或OAS的显著预测因素（所有P>0.05）。

结论

通过IHC确定的p53状态，不是Her-2/neu过表达MBC患者基于曲妥珠单抗治疗临床疗效的预测指标。