Journal of Clinical Oncology, Vol 21, Issue 3
(February), 2003: 458-462
© 2003 American Society for Clinical Oncology
HER2 Overexpression and Doxorubicin in Adjuvant Chemotherapy for Resectable Breast Cancer
Angela Moliterni,
Sylvie Ménard,
Pinuccia Valagussa,
Elia Biganzoli,
Patrizia Boracchi,
Andrea Balsari,
Patrizia Casalini,
Gorana Tomasic,
Ettore Marubini,
Silvana Pilotti,
Gianni Bonadonna
From the Medical Oncology Unit, the Molecular Targeting Unit, Department of Experimental Oncology, the Department of Pathology, Scientific Direction, Istituto Nazionale Tumori; Institute of Medical Statistics and Biometry; and Institute of Pathology, Università degli Studi di Milano, Milan, Italy.
Address reprint requests to Sylvie Ménard, PhD, Molecular Targeting Unit, Department of Experimental Oncology, Istituto Nazionale Tumori, Via Venezian 1, 20133 Milano, Italy; email: menard{at}istitutotumori.mi.it.
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; CI, 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.
Supported in part by the Associazione Italiana Ricerca sul Cancro, Milan, Italy.
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