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

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)458-462
Number of pages5
JournalJournal of Clinical Oncology
Volume21
Issue number3
DOIs
Publication statusPublished - Feb 1 2003

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Adjuvant Chemotherapy
Doxorubicin
Breast Neoplasms
Methotrexate
Fluorouracil
Cyclophosphamide
Survival
Recurrence
Neoplasms
human ERBB2 protein
Therapeutics
Therapeutic Uses
Proportional Hazards Models
Survival Rate
Monoclonal Antibodies

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Moliterni, A., Ménard, S., Valagussa, P., Biganzoli, E., Boracchi, P., Balsari, A., ... Bonadonna, G. (2003). HER2 overexpression and doxorubicin in adjuvant chemotherapy for resectable breast cancer. Journal of Clinical Oncology, 21(3), 458-462. https://doi.org/10.1200/JCO.2003.04.021

HER2 overexpression and doxorubicin in adjuvant chemotherapy for resectable breast cancer. / Moliterni, Angela; Ménard, Sylvie; Valagussa, Pinuccia; Biganzoli, Elia; Boracchi, Patrizia; Balsari, Andrea; Casalini, Patrizia; Tomasic, Gorana; Marubini, Ettore; Pilotti, Silvana; Bonadonna, Gianni.

In: Journal of Clinical Oncology, Vol. 21, No. 3, 01.02.2003, p. 458-462.

Research output: Contribution to journalArticle

Moliterni, A, Ménard, S, Valagussa, P, Biganzoli, E, Boracchi, P, Balsari, A, Casalini, P, Tomasic, G, Marubini, E, Pilotti, S & Bonadonna, G 2003, 'HER2 overexpression and doxorubicin in adjuvant chemotherapy for resectable breast cancer', Journal of Clinical Oncology, vol. 21, no. 3, pp. 458-462. https://doi.org/10.1200/JCO.2003.04.021
Moliterni, Angela ; Ménard, Sylvie ; Valagussa, Pinuccia ; Biganzoli, Elia ; Boracchi, Patrizia ; Balsari, Andrea ; Casalini, Patrizia ; Tomasic, Gorana ; Marubini, Ettore ; Pilotti, Silvana ; Bonadonna, Gianni. / HER2 overexpression and doxorubicin in adjuvant chemotherapy for resectable breast cancer. In: Journal of Clinical Oncology. 2003 ; Vol. 21, No. 3. pp. 458-462.
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T1 - HER2 overexpression and doxorubicin in adjuvant chemotherapy for resectable breast cancer

AU - Moliterni, Angela

AU - Ménard, Sylvie

AU - Valagussa, Pinuccia

AU - Biganzoli, Elia

AU - Boracchi, Patrizia

AU - Balsari, Andrea

AU - Casalini, Patrizia

AU - Tomasic, Gorana

AU - Marubini, Ettore

AU - Pilotti, Silvana

AU - Bonadonna, Gianni

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N2 - 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.

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