HER2 overexpression and doxorubicin in adjuvant chemotherapy for resectable breast cancer

被引:72
作者
Moliterni, A
Ménard, S
Valagussa, P
Biganzoli, E
Boracchi, P
Balsari, A
Casalini, P
Tomasic, G
Marubini, E
Pilotti, S
Bonadonna, G
机构
[1] Univ Milan, Ist Nazl Tumori, Mol Targeting Unit, Dept Expt Oncol, I-20133 Milan, Italy
[2] Univ Milan, Ist Nazl Tumori, Med Oncol Unit, I-20133 Milan, Italy
[3] Univ Milan, Ist Nazl Tumori, Dept Pathol Sci Direct, I-20133 Milan, Italy
[4] Univ Milan, Inst Med Stat & Biometry, I-20133 Milan, Italy
[5] Univ Milan, Inst Pathol, I-20133 Milan, Italy
关键词
D O I
10.1200/JCO.2003.04.021
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
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收藏
页码:458 / 462
页数:5
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