Neoadjuvant chemotherapy with trastuzumab followed by adjuvant trastuzumab versus neoadjuvant chemotherapy alone, in patients with HER2-positive locally advanced breast cancer (the NOAH trial): a randomised controlled superiority trial with a parallel HER2-negative cohort
Abstract
Background The monoclonal antibody trastuzumab has survival benefit when given with chemotherapy to patients with early, operable, and metastatic breast cancer that has HER2 (also known as ERBB2) overexpression or amplification. We aimed to assess event-free survival in patients with HER2-positive locally advanced or inflammatory breast cancer receiving neoadjuvant chemotherapy with or without 1 year of trastuzumab.Methods We compared 1 year of treatment with trastuzumab (given as neoadjuvant and adjuvant treatment; n=117) with no trastuzumab (118), in women with HER2-positive locally advanced or inflammatory breast cancer treated with a neoadjuvant chemotherapy regimen consisting of doxorubicin, paclitaxel, cyclophosphamide, methotrexate, and fluorouracil. Randomisation was done with a computer program and minimisation technique, taking account of geographical area, disease stage, and hormone receptor status. Investigators were informed of treatment allocation. A parallel cohort of 99 patients with HER2-negative disease was included and treated with the same chemotherapy regimen. Primary endpoint was event-free survival. Analysis was by intention to treat. This study is registered, number ISRCTN86043495.Findings Trastuzumab significantly improved event-free survival in patients with HER2-positive breast cancer (3-year event-free survival, 71% [95% CI 61-78; n=36 events] with trastuzumab, vs 56% [46-65; n=51 events] without; hazard ratio 0.59 [95% CI 0.38-0.90]; p=0.013). Trastuzumab was well tolerated and, despite concurrent administration with doxorubicin, only two patients (2%) developed symptomatic cardiac failure. Both responded to cardiac drugs.Interpretation The addition of neoadjuvant and adjuvant trastuzumab to neoadjuvant chemotherapy should be considered for women with HER2-positive locally advanced or inflammatory breast cancer to improve event-free survival, survival, and clinical and pathological tumour responses.Funding F Hoffmann-La Roche.
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Achievement of a pathological complete response (path CR) in the breast and axillary lymph nodes after neoadjuvant trastuzumab or chemotherapy has been associated with improved long-term outcome.
“Achievement of a pathological complete response (path CR) in the breast and axillary lymph nodes after neoadjuvant trastuzumab or chemotherapy has been associated with improved long-term outcome (Gianni et al., 2010; Liedtke et al., 2008).”
From ERBB Receptors: From Oncogene Discovery to Basic Science to Mechanism-Based Cancer Therapeutics (2014) · cites this paper as Gianni et al., 2010
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- Authors
- Gianni, L., Eiermann, W., Semiglazov, V., Manikhas, A., Lluch, A., Tjulandin, S., Zambetti, M., Vazquez, F., Byakhow, M., Lichinitser, M., Climent, M. A., Ciruelos, E., Ojeda, B., Mansutti, M., Bozhok, A., Baronio, R., Feyereislova, A., Barton, C., Valagussa, P., & Baselga, J.
- Affiliations
- Fondazione IRCCS Istituto Nazionale dei Tumori (IT)
- Rotkreuzklinikum München (DE)
- City Clinical Oncology Center (RU)
- Hospital Clínico Universitario de Valencia (ES)
- Russian Cancer Research Center NN Blokhin (RU)
- Vall d'Hebron Hospital Universitari (ES)
- Central Clinical Hospital No 2 named Semashko (RU)
- Hospital Universitario 12 De Octubre (ES)
- Ospedale Santa Maria della Misericordia di Udine (IT)
- Fondazione Michelangelo (IT)
- F. Hoffmann-La Roche AG (CH)
- Corresponding author
- Gianni, Luca
- ORCID
- Venue
- The Lancet
- Publisher
- Elsevier BV
- Published
- 2010-01
- Volume
- 375
- Issue
- 9712
- Pages
- 377-384
- ISSN
- 0099-5355 (ISSN-L)
- 0140-6736
- OpenAlex
- W1987326983
- Cited by
- 1,255
- References
- 35
- Citations by year
- 2026: 27 · 2025: 54 · 2024: 64 · 2023: 70 · 2022: 59 · 2021: 83 · 2020: 77 · 2019: 74 · 2018: 75 · 2017: 76 · 2016: 85 · 2015: 82 · 2014: 110 · 2013: 104 · 2012: 89
- FWCI
- 49.89
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Lancet (publishedVersion)
- PubMed (publishedVersion)
- 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, locally advanced breast cancer, inflammatory breast cancer, neoadjuvant chemotherapy, adjuvant trastuzumab, event-free survival, doxorubicin, paclitaxel, cyclophosphamide, methotrexate, 5-fluorouracil, cardiotoxicity, HER2-negative breast cancer
- MeSH terms
- Trastuzumab, Adenocarcinoma, Adult, Antibodies, Monoclonal, Antineoplastic Combined Chemotherapy Protocols, Breast Neoplasms, Combined Modality Therapy, Cyclophosphamide, Doxorubicin, Female, Fluorouracil, Follow-Up Studies, Humans, Infusions, Intravenous, Methotrexate, Middle Aged, Prospective Studies, Time Factors, Proportional Hazards Models, Chemotherapy, Adjuvant, Paclitaxel, Disease-Free Survival, Erb-b2 Receptor Tyrosine Kinases, Genes, erbB-2, Neoadjuvant Therapy, Antibodies, Monoclonal, Humanized
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