C-ERBB-2 EXPRESSION AND RESPONSE TO ADJUVANT THERAPY IN WOMEN WITH NODE-POSITIVE EARLY BREAST-CANCER
C-ERBB-2 EXPRESSION AND RESPONSE TO ADJUVANT THERAPY IN WOMEN WITH NODE-POSITIVE EARLY BREAST-CANCER
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DOI：
10.1056/nejm199405053301802
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发表时间：
1994-05-05
影响因子：
158.5
通讯作者：
HENDERSON, IC
中科院分区：
文献类型：
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作者：
MUSS, HB;THOR, AD;HENDERSON, IC
背景分子标志物在预测乳腺癌治疗反应中的作用尚不明确。癌症和白血病组B（CALGB）在1572名淋巴结阳性乳腺癌女性中进行了一项随机化化疗试验（CALGB 8541），比较了3种剂量（高、中、低）的环磷酰胺、阿霉素和氟尿嘧啶。本研究（CALGB 8869）旨在确定DNA指数、S期分数、c-erbB-2表达或p53积累是否可用作标记物，以识别比其他患者更有可能从高剂量化疗中获益的患者亚组。组织块从大型CALGB试验中随机选择的442名患者中获得。分析原发病灶石蜡切片的DNA含量、S期细胞比例、c-erbB-2表达和p53积聚。如果患者的肿瘤有c-erbB-2过表达，则随机分配到高剂量辅助化疗方案的患者的无病生存期和总生存期显著延长。通过将S期分数或p53蓄积的数据添加到分析中，未获得更多信息。在c-erbB-2表达极低或无表达的患者中，没有明确的剂量反应效应证据。环磷酰胺、阿霉素和氟尿嘧啶辅助化疗在c-erbB-2过表达的患者中有显著的剂量反应效应，但在无c-erbB-2表达或极低c-erbB-2表达的患者中无此效应。c-erbB-2过表达可能是一个有用的标志物，以确定谁是最有可能受益于大剂量的辅助化疗的患者。
Background. The role of molecular markers in predicting the response to treatment of breast cancer is poorly defined. The Cancer and Leukemia Group B (CALGB) conducted a randomized adjuvant-chemotherapy trial (CALGB 8541) comparing three doses (high, moderate, and low) of cyclophosphamide, doxorubicin, and fluorouracil in 1572 women with node-positive breast cancer. This study (CALGB 8869) was designed to determine whether the DNA index, the S-phase fraction, c-erbB-2 expression, or p53 accumulation could be used as a marker to identify a subgroup of patients more likely than others to benefit from high doses of chemotherapy.Methods. Tissue blocks were obtained from 442 patients randomly selected from the larger CALGB trial. Paraffin sections from the primary lesions were analyzed for DNA content, S-phase fraction, c-erbB-2 expression, and p53 accumulation.Results. Patients randomly assigned to the high-dose regimen of adjuvant chemotherapy had significantly longer disease-free and overall survival if their tumors had c-erbB-2 overexpression. No further information was gained by adding the data on S-phase fraction or p53 accumulation to the analysis. There was no clear evidence of a dose-response effect in patients with minimal or no c-erbB-2 expression.Conclusions. There is a significant dose-response effect of adjuvant chemotherapy with cyclophosphamide, doxorubicin, and fluorouracil in patients with overexpression of c-erbB-2 but not in patients with no c-erbB-2 expression or minimal c-erbB-2 expression. Overexpression of c-erbB-2 may be a useful marker to identify the patients who are most likely to benefit from high doses of adjuvant chemotherapy.