Serum HER2 extracellular domain in metastatic breast cancer patients treated with weekly trastuzumab and paclitaxel: association with HER2 status by immunohistochemistry and fluorescence in situ hybridization and with response rate

Serum HER2 extracellular domain in metastatic breast cancer patients treated with weekly trastuzumab and paclitaxel: association with HER2 status by immunohistochemistry and fluorescence in situ hybridization and with response rate
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DOI:
10.1093/annonc/mdi059
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发表时间:
2005-02-01
期刊:
影响因子:
50.5
通讯作者:
Hudis, C
Hudis, C
中科院分区:
医学1区
文献类型:
--
作者:
Fornier, MN;Seidman, AD;Hudis, C

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目的:我们通过免疫组化(IHC)和荧光原位杂交(FISH)研究了循环HER2胞外区(ECD)和组织HER2状态之间的关系。我们还研究了它的预测价值在一个队列的转移性乳腺癌患者每周治疗曲妥珠单抗和paclitaxel.Methods:符合条件的患者有治疗前和治疗后储存的血清标本,并在先前报道的II期试验治疗。回顾性分析评价:结果:95例患者中有55例(58%)的血清标本保存完好。通过IHC和FISH评估的HER2状态与基线血清HER2 ECD水平之间存在统计学显著相关性。治疗12周后ECD恢复正常的患者与ECD水平持续升高的患者相比,应答比例更高(68%对15%,P=0.005)。从基线HER2 ECD的相对下降超过55%的预测responsibilitytotherapy.Conclusion:一个统计学显着的关联,观察到治疗前血清HER2 ECD和组织HER2状态之间的评估IHC和FISH。血清HER2 ECD水平降低是对基于曲妥珠单抗的治疗应答的显著预测因子。
Purpose: We explored the relationship between circulating HER2 extracellular domain (ECD) and tissue HER2 status as determined by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). We also examined its predictive value in a cohort of metastatic breast cancer patients treated with weekly trastuzumab and paclitaxel.Methods: Eligible patients had pre- and post-treatment stored serum specimens and were treated on a previously reported phase II trial. Retrospective analysis evaluated: the association between pretreatment serum HER2 ECD and tissue HER2 status by IHC and FISH; and the association between change in serum HER2 ECD after 12 weeks of therapy and response proportion.Results: Stored serum samples were available for 55/95 (58%) patients. Statistically significant associations were found between HER2 status as assessed by IHC and FISH, and baseline serum HER2 ECD level. Patients whose ECD normalized after 12 weeks of therapy had a higher response proportion compared with patients with persistently high ECD levels (68% versus 15%, P=0.005). A relative decline of over 55% from baseline HER2 ECD predicted response to therapy.Conclusion: A statistically significant association was observed between pretreatment serum HER2 ECD and tissue HER2 status as assessed by IHC and FISH. A decrease in serum HER2 ECD level was a significant predictor of response to trastuzumab-based therapy.