Comparison of methods of measuring HER-2 in metastatic breast cancer patients treated with high-dose chemotherapy
Comparison of methods of measuring HER-2 in metastatic breast cancer patients treated with high-dose chemotherapy
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DOI：
10.1200/jco.2001.19.6.1698
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发表时间：
2001-03-15
影响因子：
45.3
通讯作者：
Bentley, RC
中科院分区：
文献类型：
--
作者：
Harris, LN;Liotcheva, V;Bentley, RC
目的：HER-2在20%至30%的人类乳腺癌中过表达，并与不良预后相关。研究表明HER-2过表达与对烷基化剂的抗性之间存在关联。为了进一步评估这种关系，我们评估了HER-2的相互作用，通过不同的方法测量，以及转移性乳腺癌中烷基化剂剂量增强后的结果。患者和方法：从1988年到1995年，杜克大学的425例转移性乳腺癌患者在阿霉素基础治疗（AFM）后加入了高剂量烷基化剂（HDC）和自体细胞支持的研究。采用免疫组化（IHC）和荧光原位杂交（FISH）技术检测HER-2在血清细胞外结构域（ECD）和组织中的含量。结果：HER-2 ECD在afm前的29%（65 / 19）和hdc前的11.7%（290 / 34）中呈阳性。较高的afm前和较高的hdc前HER-2 ECD预测较差的总生存（P = 0.045和P = 0.0096）。HER-2在IHC和FISH中的过表达与更差的无病生存或总生存没有相关性。FISH和ECD对IHC具有高度特异性（分别为97.3%和97.7%）。然而，ECD对免疫组化的敏感性较低——只有22%的HER-2原发肿瘤患者将ECD释放到血清中。结论：这些数据提示HER-2的测定方法对预测临床预后有重要意义。HER2 ECD可以识别HER2阳性肿瘤的预后不良亚组。IHC/FISH缺乏HER2与较差预后的相关性表明，AFM和/或HDC治疗可能能够克服这一预后因素的影响，或者它可能不是这种情况下的预后因素。(C) 2001年美国临床肿瘤学会。
Purpose: HER-2 is overexpressed in 20% to 30% of human breast cancer and is associated with poor outcome. Studies suggest an association between HER-2 overexpression and resistance to alkylating agents. To further evaluate this relationship, we assessed the interaction of HER-2, measured by different methods, and outcome after dose intensification with alkylating agents in metastatic breast cancer.Patients and Methods: From 1988 to 1995 at Duke University, 425 patients with metastatic breast cancer were enrolled in a study of high-dose alkylating agents (HDC) with autologous cellular support after doxorubicin-based therapy (AFM). HER-2 was measured in serum for shed extracellular domain (ECD) and in tissue by immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH).Results: HER-2 ECD was positive in 29%(19 of 65) of patients pre-AFM and in 11.7% (34 of 290) pre-HDC. Higher pre-AFM and higher pre-HDC HER-2 ECD predicted worse overall survival (P =.045 and P =.0096, respectively). HER-2 overexpression by IHC and FISH showed no correlation with worse disease-free survival or overall survival. FISH and ECD were highly specific for IHC (97.3% and 97.7% respectively). However, ECD had a low sensitivity for IHC- only 22% of patients with HER-2 in the primary tumor shed ECD into the serum.Conclusion: These data suggest that the method of measuring HER-2 is important in predicting clinical outcome. HER2 ECD may identify a poor prognosis subgroup of HER-2-positive tumors. Lack of association of HER2 by IHC/FISH with worse outcome suggests that therapy with AFM and/or HDC therapy may be able to overcome the effect of this prognostic factor or it may not be a prognostic factor in this setting. (C) 2001 by American Society of Clinical Oncology.