评估 HER2 和 p53 表达在预测晚期乳腺癌患者对基于多西紫杉醇的一线化疗反应中的作用。
Evaluation of HER2 and p53 expression in predicting response to docetaxel-based first-line chemotherapy in advanced breast cancer.
机构信息
Oncology Department, Medical Oncology Division, AUSL12 di Viareggio and Istituto Toscano Tumori-Versilia Hospital, Lido di Camaiore, Italy.
出版信息
J Exp Clin Cancer Res. 2011 Apr 11;30(1):38. doi: 10.1186/1756-9966-30-38.
BACKGROUND
The human epidermal growth factor receptor 2 (HER2) and p53 pathways may be involved in chemotherapy sensitivity and/or resistance. We explore the value of HER2 and p53 status to foretell docetaxel sensitivity in advanced breast cancer.
METHODS
HER2 and p53 expression was analysed in 36 (median age 55 yrs; range 37-87) metastatic breast cancer patients receiving docetaxel-based first-line chemotherapy. HER2 was determined by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), p53 was tested by IHC. We correlate the expression of study parameters with pathologic parameters, RECIST response and survival. The standard cut-off value of 2 was used to determine HER2 overexpression while p53 mean expression level was used to divide low/high expressors tumors.
RESULTS
Median time to progression and overall survival were 9 (range 2-54) and 20 (range 3-101) months. Overall response rate was 41.6%. Nine cases showed HER2 overexpression. HER2 was more frequently overexpressed in less differentiated (p=0.05) and higher stage (p=0.003) disease. Mean FISH-HER2 values were significantly higher in responder than in non-responder pts (8.53±10.21 vs 2.50±4.12, p=0.027). Moreover, HER2 overexpression correlates with treatment response at cross-tabulation analysis (p=0.046). p53 expression was only associated with higher stage disease (p=0.02) but lack of any significant association with HER status or docetaxel response. No significant relation with survival was observed for any parameter.
CONCLUSION
Our data seem to indicate that FISH-determined HER2 status but not p53 is associated with docetaxel sensitivity in metastatic breast cancer.
背景
人类表皮生长因子受体 2（HER2）和 p53 通路可能参与化疗敏感性和/或耐药性。我们探讨 HER2 和 p53 状态在预测晚期乳腺癌中多西紫杉醇敏感性的价值。
方法
对 36 例（中位年龄 55 岁；范围 37-87）接受基于多西紫杉醇的一线化疗的转移性乳腺癌患者进行 HER2 和 p53 表达分析。HER2 通过免疫组化（IHC）和荧光原位杂交（FISH）确定，p53 通过 IHC 检测。我们将研究参数的表达与病理参数、RECIST 反应和生存相关联。使用 2 的标准截断值来确定 HER2 过表达，而使用 p53 平均表达水平来划分低/高表达肿瘤。
结果
中位无进展生存期和总生存期分别为 9（范围 2-54）和 20（范围 3-101）个月。总缓解率为 41.6%。9 例出现 HER2 过表达。HER2 在分化程度较低（p=0.05）和分期较高（p=0.003）的疾病中更常过表达。在应答者中，FISH-HER2 值的平均值显著高于无应答者（8.53±10.21 与 2.50±4.12，p=0.027）。此外，在交叉表分析中，HER2 过表达与治疗反应相关（p=0.046）。p53 表达仅与较高的分期疾病相关（p=0.02），但与 HER 状态或多西紫杉醇反应无关。任何参数与生存均无显著关系。
结论
我们的数据似乎表明，FISH 确定的 HER2 状态而不是 p53 与转移性乳腺癌中多西紫杉醇的敏感性相关。
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