Trastuzumab after Adjuvant Chemotherapy in HER2-Positive Breast Cancer
Open accessAbstract
BACKGROUND: Trastuzumab, a recombinant monoclonal antibody against HER2, has clinical activity in advanced breast cancer that overexpresses HER2. We investigated its efficacy and safety after excision of early-stage breast cancer and completion of chemotherapy. METHODS: This international, multicenter, randomized trial compared one or two years of trastuzumab given every three weeks with observation in patients with HER2-positive and either node-negative or node-positive breast cancer who had completed locoregional therapy and at least four cycles of neoadjuvant or adjuvant chemotherapy. RESULTS: Data were available for 1694 women randomly assigned to two years of treatment with trastuzumab, 1694 women assigned to one year of trastuzumab, and 1693 women assigned to observation. We report here the results only of treatment with trastuzumab for one year or observation. At the first planned interim analysis (median follow-up of one year), 347 events (recurrence of breast cancer, contralateral breast cancer, second nonbreast malignant disease, or death) were observed: 127 events in the trastuzumab group and 220 in the observation group. The unadjusted hazard ratio for an event in the trastuzumab group, as compared with the observation group, was 0.54 (95 percent confidence interval, 0.43 to 0.67; P<0.0001 by the log-rank test, crossing the interim analysis boundary), representing an absolute benefit in terms of disease-free survival at two years of 8.4 percentage points. Overall survival in the two groups was not significantly different (29 deaths with trastuzumab vs. 37 with observation). Severe cardiotoxicity developed in 0.5 percent of the women who were treated with trastuzumab. CONCLUSIONS: One year of treatment with trastuzumab after adjuvant chemotherapy significantly improves disease-free survival among women with HER2-positive breast cancer. (ClinicalTrials.gov number, NCT00045032.)
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In the field testing, chemotherapy with or without trastuzumab in (neo)adjuvant HER-2-positive breast cancer was assigned ESMO-MCBS grade A.
“Chemotherapy ± trastuzumab | HERA | (Neo)adjuvant HER-2- | DFS | 2-year DFS | 8.40% | 0.54 (0.43-0.67) | | | | | A | [ 56]”
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- Authors
- Piccart-Gebhart, M. J., Procter, M., Leyland-Jones, B., Goldhirsch, A., Untch, M., Smith, I., Gianni, L., Baselga, J., Bell, R., Jackisch, C., Cameron, D., Dowsett, M., Barrios, C. H., Steger, G., Huang, C.-S., Andersson, M., Inbar, M., Lichinitser, M., Láng, I., Nitz, U., Iwata, H., Thomssen, C., Lohrisch, C., Suter, T. M., Rüschoff, J., Sütő, T., Greatorex, V., Ward, C., Straehle, C., McFadden, E., Dolci, M. S., & Gelber, R. D.
- Affiliations
- European Institute of Oncology (IT)
- McGill University (CA)
- Istituto Oncologico della Svizzera Italiana (CH)
- Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe (DE)
- Institute of Cancer Research (GB)
- Fondazione IRCCS Istituto Nazionale dei Tumori (IT)
- Vall d'Hebron Hospital Universitari (ES)
- Geelong Hospital (AU)
- Philipps University of Marburg (DE)
- Western General Hospital (GB)
- National Health Service (GB)
- Hospital São Lucas da PUCRS (BR)
- Medical University of Vienna (AT)
- Rigshospitalet (DK)
- Tel Aviv Sourasky Medical Center (IL)
- Russian Cancer Research Center NN Blokhin (RU)
- National Institute of Oncology (HU)
- Heinrich Heine University Düsseldorf (DE)
- Aichi Cancer Center (JP)
- University Medical Center Hamburg-Eppendorf (DE)
- BC Cancer Agency (CA)
- Klinikum Kassel (DE)
- F. Hoffmann-La Roche AG (CH)
- Breast International Group (BE)
- Université Libre de Bruxelles (BE)
- Dana-Farber Cancer Institute (US)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2005-10-20
- Volume
- 353
- Issue
- 16
- Pages
- 1659-1672
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2149908785
- Cited by
- 5,084
- References
- 1
- Citations by year
- 2026: 76 · 2025: 110 · 2024: 135 · 2023: 155 · 2022: 213 · 2021: 184 · 2020: 193 · 2019: 177 · 2018: 199 · 2017: 243 · 2016: 225 · 2015: 311 · 2014: 269 · 2013: 327 · 2012: 265
- FWCI
- 151.85
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion)
- The HKU Scholars Hub (University of Hong Kong) (submittedVersion)
- Topics
- Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Gastric Cancer Management and Outcomes
- Keywords
- trastuzumab, HER2-positive breast cancer, adjuvant chemotherapy, neoadjuvant chemotherapy, disease-free survival, overall survival, cardiotoxicity, early breast cancer, HER2-targeted therapy
- MeSH terms
- Trastuzumab, Adult, Antibodies, Monoclonal, Antineoplastic Agents, Breast Neoplasms, Combined Modality Therapy, Female, Heart Diseases, Humans, Middle Aged, Recurrence, Survival Analysis, Chemotherapy, Adjuvant, Disease-Free Survival, Erb-b2 Receptor Tyrosine Kinases, Receptor, ErbB-2, Antibodies, Monoclonal, Humanized
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