erbB-2, p53, and efficacy of adjuvant therapy in lymph node-positive breast cancer
erbB-2, p53, and efficacy of adjuvant therapy in lymph node-positive breast cancer
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DOI：
10.1093/jnci/90.18.1346
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发表时间：
1998-09-16
影响因子：
10.3
通讯作者：
Liu, ET
中科院分区：
文献类型：
--
作者：
Thor, AD;Berry, DA;Liu, ET
背景：我们之前报道了erbB-2基因（也称为HER-2/neu和ERBB2）在乳腺癌中的高表达与患者对环磷酰胺、阿霉素（阿霉素）和5-氟尿嘧啶（CAF）剂量强化治疗的反应有关，这是基于对397例腋窝淋巴结阳性肿瘤患者（A组）的短期随访，这些患者参加了癌症和白血病B组（CALGB）方案8541。方法：为了验证这些发现，Foe在CALGB 8541的另一组595例患者（B组）中进行了erbB-2和p53蛋白表达的免疫组织化学分析，以及所有患者（a组和B组）肿瘤中erbB-2基因扩增的分子分析，将Marker数据与临床、组织学、治疗和结局数据进行比较。结果：A组数据的最新分析（中位随访10.4年）显示，通过免疫组织化学或分子数据，erbB-2表达与CAF剂量之间的相互作用甚至更强。在所有992例患者中观察到erbB-2表达与CAF剂量之间的类似相互作用，作为单一组进行分析。然而，对于单独的B组（中位随访，8.2年），统计分析方法的结果有所不同，通过使用比例风险模型，erbB-2表达与caf剂量的相互作用在所有患者中并不显著，然而，在随机分配到高剂量组或中剂量组的患者亚组中，具有显著性。当使用预后指数调整患者数据的差异时（以平衡低剂量组随机化的明显失败），erbB-2表达与CAF剂量的相互作用在验证集B的所有患者中也很显著，p53免疫阳性与CAF剂量之间也存在相互作用。结论：erbB-2高表达乳腺肿瘤患者受益于剂量强化CAF的假设在临床实施前需要进一步验证。erbB-2表达、p53表达和CAF剂量之间的相互作用强调了预测标记物的复杂性，多重相互作用可能会混淆结果。
Background: We have previously reported that high expression of the erbB-2 gene (also known as HER-2/neu and ERBB2) in breast cancer is associated with patient response to dose-intensive treatment with cyclophosphamide, doxorubicin (Adriamycin), and 5-flurouracil (CAF) on the basis of short-term follow-up of 397 patients (set A) with axillary lymph node-positive tumors who were enrolled in Cancer and Leukemia Group B (CALGB) protocol 8541. Methods: To validate those findings, Foe conducted immunohistochemical analyses of erbB-2 and p53 protein expression in an additional cohort of 595 patients (set B) from CALGB 8541, as well as a molecular analysis of erbB-2 gene amplification in tumors from all patients (sets A and B), Marker data were compared with clinical, histologic, treatment, and outcome data. Results: Updated analyses of data from set A (median follow-up, 10.4 years) showed an even stronger interaction between erbB-2 expression and CAF dose, by use of either immunohistochemical or molecular data. A similar interaction between erbB-2 expression and CAF dose was observed in ail 992 patients, analyzed as a single group. However, for set B alone (median follow-up, 8.2 years), results varied with the method of statistical analysis, By use of a proportional hazards model, the erbB-2 expression-CAF dose interaction was not significant for all patients, However, in the subgroups of patients randomly assigned to the high- or the moderate-dose arms, significance was achieved. When patient data were adjusted for differences by use of a prognostic index (to balance an apparent failure of randomization in the low-dose arm), the erbB-2 expression-CAF dose interaction was significant in all patients from the validation set B as well, An interaction was also observed between p53 immunopositivity and CAF dose. Conclusions: The hypothesis that patients: whose breast tumors exhibit high erbB-2 expression benefit from dose-intensive CAF should be further validated before clinical implementation. Interactions between erbB-2 expression, p53 expression, and CAF dose underscore the complexities of predictive markers where multiple interactions may confound the outcome.