Circulating HER 2 Extracellular Domain and Resistance to Chemotherapy in Advanced Breast Cancer 1
Circulating HER 2 Extracellular Domain and Resistance to Chemotherapy in Advanced Breast Cancer 1
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晚期乳腺癌中循环 HER 2 胞外结构域和化疗耐药性 1
DOI：
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Carlos Fonfach
中科院分区：
文献类型：
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作者：
R. Sánchez;Emil Schneider;Gustavo Martínez;Carlos Fonfach
为了检验HER 2与化疗耐药之间相关性的假设，我们在一项使用紫杉醇和多柔比星的多中心II期试验中对晚期乳腺癌患者循环HER 2胞外结构域（ECD）的预测价值进行了前瞻性评估。从58例晚期疾病一线化疗前的转移性乳腺癌患者中收集血清样本，并使用酶免疫测定法测量循环HER 2 ECD水平。用抗HER 2单克隆抗体CB 11的免疫组织化学法评估原发性肿瘤中HER 2的过表达。当450 fmol/ml作为临界值时，24例（41%）HER 2 ECD水平升高。循环HER 2 ECD水平升高与原发性肿瘤组织中HER 2的表达和转移性肿瘤负荷相关（分别用标志物CA 15-3评价; P 5 0. 032和P 5 0. 002），但与绝经状态、诊断分期、既往辅助治疗或转移部位数量等变量无关。循环HER 2 ECD水平与治疗应答呈负相关。HER 2 ECD水平升高的患者（0%; 95%置信区间，0-13%）获得化疗完全缓解的概率显著低于HER 2水平未升高的患者（26%; 95%置信区间，12-45%）（P <5 0.021）。此外，HER 2 ECD升高患者的临床应答持续时间显著短于HER 2未升高患者（7.5 vs 11个月; P 5 0.035）。总之，转移性乳腺癌患者的循环HER 2 ECD水平升高与紫杉醇-多柔比星化疗组合的疗效降低相关。我们认为，在晚期乳腺癌中，与HER 2表达相关的不良反应率可能无法通过单独的积极化疗逆转。
To test the hypothesis of an association between HER2 and chemotherapy resistance, we performed a prospective assessment of the predictive value of the circulating HER2 extracellular domain (ECD) in patients with advanced breast carcinoma in the setting of a multicenter Phase II trial using paclitaxel and doxorubicin. Serum samples were collected from 58 patients with metastatic breast carcinoma before first-line chemotherapy for advanced disease, and the levels of circulating HER2 ECD were measured using an enzyme immunoassay. Immunohistochemistry with antiHER2 monoclonal antibody CB11 was used to assess the overexpression of HER2 in the primary tumors. When 450 fmol/ml was used as a cutoff, 24 cases (41%) had elevated HER2 ECD levels. Elevated levels of circulating HER2 ECD were associated with the expression of HER2 in the primary tumor tissue and with the metastatic tumor burden (evaluated with the marker CA 15-3; P 5 0.032 andP 5 0.002, respectively) but not with variables such as menopausal status, stage at diagnosis, previous adjuvant therapy, or the number of metastatic sites. The levels of circulating HER2 ECD correlated inversely with the response to treatment. The probability of obtaining a complete response to chemotherapy was significantly lower (P 5 0.021) in patients with elevated HER2 ECD levels (0%; 95% confidence interval, 0–13%) compared with patients with nonelevated HER2 (26%; 95% confidence interval, 12–45%). In addition, the duration of clinical response was significantly shorter in patients with elevated HER2 ECD, compared with the cases with nonelevated HER2 (7.5versus11 months; P 5 0.035). In conclusion, elevated levels of circulating HER2 ECD in patients with metastatic breast cancer correlate with reduced efficacy of a paclitaxel-doxorubicin chemotherapy combination. We suggest that the poor response rate associated with HER2 expression in advanced breast cancer may not be reversed by aggressive chemotherapy alone.
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DOI：
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发表时间：
1997-04
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
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作者：
A. Makris;T. Powles;M. Dowsett;C. Osborne;P. Trott;I. Fernando;S. Ashley;M. Ormerod;J. Titley;R. Gregory;D. Allred
通讯作者：
A. Makris;T. Powles;M. Dowsett;C. Osborne;P. Trott;I. Fernando;S. Ashley;M. Ormerod;J. Titley;R. Gregory;D. Allred
影响因子：
158.5
作者：
MUSS, HB;THOR, AD;HENDERSON, IC
通讯作者：
HENDERSON, IC
DOI：
10.1007/bf02838363
发表时间：
2004-03-01
影响因子：
1.100
作者：
Cao Ming-li;Liu Shi-zhen;Yu Yong-fu
通讯作者：
Yu Yong-fu
影响因子：
10.3
作者：
Paik, SM;Bryant, J;Wolmark, N
通讯作者：
Wolmark, N
档案组织样本中 HER-2/neu 抗体的敏感性：癌基因表达免疫组织化学研究中潜在的错误来源。
影响因子：
11.2
作者：
Press,MF;Hung,G;Godolphin,W;Slamon,DJ
通讯作者：
Slamon,DJ