HER2 overexpression and doxorubicin in adjuvant chemotherapy for resectable breast cancer
HER2 overexpression and doxorubicin in adjuvant chemotherapy for resectable breast cancer
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DOI：
10.1200/jco.2003.04.021
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发表时间：
2003-02-01
影响因子：
45.3
通讯作者：
Bonadonna, G
中科院分区：
文献类型：
--
作者：
Moliterni, A;Ménard, S;Bonadonna, G
目的：人表皮生长因子受体2（HER 2）过表达被发现预测乳腺癌患者用阿霉素（阿霉素[ADM]）治疗的良好反应。我们最近研究的证据表明，淋巴结阳性患者对环磷酰胺、甲氨蝶呤和氟尿嘧啶（CMF）有反应，而与HER 2状态无关。我们解决的问题，是否治疗方案，包括CMF和ADM与CMF单独与HER 2+和HER 2-肿瘤患者的无复发生存期（RFS）和总生存期（OS）方面具有相同的治疗效果。方法：存档标本的原发性肿瘤从506例患者在一项前瞻性临床试验中进行了染色与抗HER 2单克隆抗体CB 11。最初，患者被随机分配接受12个疗程的静脉CMF或8个疗程的相同方案，随后接受4个周期的ADM。RFS和OS通过考克斯模型进行分析，该模型考虑了治疗、HER 2状态以及治疗与HER 2状态之间的相互作用，并调整了其他已知临床和生物病理学因素的影响。生存率分析表明，根据HER 2状态分组的患者中可能存在治疗差异效应。与CMF单药治疗相比，CMF联合ADM治疗后，在HER 2+亚组中观察到RFS和OS改善。中位随访时间为15年，RFS的风险比（HR）在HER 2+肿瘤中为0.83，在HER 2-肿瘤中为1.22。结论：ADM联合CMF对HER 2+肿瘤患者的生存率有明显的改善作用（HR = 0.61; CI为0.32 ~ 1.16），而对HER 2-患者的生存率无明显影响（HR = 1.26）。(C)2003年，美国临床肿瘤学会。
Purpose: Human epidermal growth factor receptor 2 (HER2) overexpression was found to predict a good response in breast carcinoma patients treated with doxorubicin (Adriamycin [ADM]). Evidence from our recent study indicates that node-positive patients respond to cyclophosphamide, methotrexate, and fluorouracil (CMF) regardless of HER2 status. We address the issue of whether therapy regimens including CMF and ADM versus CMF alone have the same therapeutic effect in patients with HER2+ and HER2- tumors in terms of relapse-free survival (RFS) and overall survival (OS).Methods: Archival specimens of the primary tumors from 506 patients in a prospective clinical trial were stained with the anti-HER2 monoclonal antibody CB11. Originally, patients were randomly allocated to receive either 12 courses of intravenous CMF or eight courses of the same regimen followed by four cycles of ADM. RFS and OS were analyzed by a Cox model taking into account treatment, HER2 status, and the interaction between treatment and HER2 status, adjusting for the effect of other known clinical and biopathologic factors.Results: Analysis of survival rates indicates a possible differential effect of treatment in the patients grouped according to HER2 status. Improved RFS and OS were observed in the HER2+ subgroup after treatment with CMF plus ADM versus CMF alone. With a median follow-up of 15 years, the hazard ratio (HR) for RFS was 0.83 in HER2+ tumors and 1.22 in HER2- tumors. The effect of treatment was more evident on OS in HER2+ patients (HR = 0.61; Cl, 0.32 to 1.16) than in HER2- patients (HR = 1.26).Conclusion: Our data indicate that adding ADM to CMF might be beneficial for patients with HER2+ tumors. (C) 2003 by American Society of Clinical Oncology.