Prognostic and predictive implications of HER2/ERBB2/neu gene mutations in lung cancers

Tomizawa, Kenji; Suda, Kenichi; Onozato, Ryoichi; Kosaka, Takayuki; Endoh, Hideki; Sekido, Yoshitaka; Shigematsu, Hisayuki; Kuwano, Hiroyuki; Yatabe, Yasushi; Mitsudomi, Tetsuya

doi:10.1016/j.lungcan.2011.01.014

Cited by 151Lung Cancer Treatments and MutationsHER2/EGFR in Cancer ResearchLung Cancer Research Studies

Prognostic and predictive implications of HER2/ERBB2/neu gene mutations in lung cancers

Tomizawa, Kenji, Suda, Kenichi, Onozato, Ryoichi, Kosaka, Takayuki, Endoh, Hideki, Sekido, Yoshitaka, Shigematsu, Hisayuki, Kuwano, Hiroyuki +2 more·2011·Lung Cancer

DOI 10.1016/j.lungcan.2011.01.014

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Abstract

Background Activating mutation in the kinase domain of the human EGF receptor 2 (HER2) gene (also known as ERBB2 or neu) is reported to be present in a small fraction of lung adenocarcinomas. However its prognostic and predictive implications are not yet established.Patients and methods We examined 504 Japanese lung cancer patients who underwent pulmonary resection for HER2 mutations by direct sequencing and evaluated their prognostic and predictive implications. Updated prognostic data of 14 Japanese patients with HER2 mutation from previous two reports were also gathered.Results HER2 mutations were identified in 13 of 504 cases (2.6%). Patients with HER2 mutations were common in female, nonsmokers and adenocarcinomas as those with EGFR mutations. When confined to the subgroup of nonsmokers with adenocarcinoma or adenosquamous cell carcinoma without EGFR mutations, the frequency of HER2 mutations was 14.1% (11/78). There was no difference in the overall survival of patients with HER2 mutations, compared with patients harboring EGFR mutations and patients harboring wild types for both EGFR and HER2. Within the patients with HER2 mutation, two of three with TP53 mutation and one of 13 without TP53 mutation died of the disease, suggesting negative prognostic role of the TP53 mutation. Three patients with HER2 mutations did not respond to platinum-based chemotherapy and EGFR-TKIs. Of note, one patient with the most common HER2 mutations, YVMA776-779ins, responded to trastuzumab plus vinorelbine after failure of multiple round of platinum-based chemotherapy and gefitinib.Conclusion HER2 mutations are present in a subset of patients with lung cancer having distinct clinical features. HER2 mutations were not associated with the prognosis of patients with lung cancers. Patients with HER2 mutations might benefit from anti-HER2 therapy.

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The A775_G776insYVMA mutation accounts for most HER2 exon 20 mutations observed in NSCLC.
“with the A775_G776insYVMA mutation accounting for most of the mutations seen in NSCLC (17–21).”
From Response Heterogeneity of EGFR and HER2 Exon 20 Insertions to Covalent EGFR and HER2 Inhibitors (2017) · cites this paper as [20]

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Authors: Tomizawa, K., Suda, K., Onozato, R., Kosaka, T., Endoh, H., Sekido, Y., Shigematsu, H., Kuwano, H., Yatabe, Y., & Mitsudomi, T.
Affiliations: Gunma University (JP)
Aichi Cancer Center (JP)
Okayama Medical Center (JP)
Corresponding author: Mitsudomi, Tetsuya
ORCID: Tomizawa, Kenji
Suda, Kenichi
Onozato, Ryoichi
Kosaka, Takayuki
Endoh, Hideki
Sekido, Yoshitaka
Kuwano, Hiroyuki
Yatabe, Yasushi
Mitsudomi, Tetsuya
Venue: Lung Cancer
Publisher: Elsevier BV
Published: 2011-10
Volume: 74
Issue: 1
Pages: 139-144
ISSN: 0169-5002 (ISSN-L)
DOI: 10.1016/j.lungcan.2011.01.014
OpenAlex: W2107002118
Cited by: 151
References: 33
Citations by year: 2026: 2 · 2025: 9 · 2024: 8 · 2023: 10 · 2022: 7 · 2021: 8 · 2020: 10 · 2019: 2 · 2018: 11 · 2017: 12 · 2016: 12 · 2015: 16 · 2014: 13 · 2013: 13 · 2012: 13
FWCI: 11.99
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Lung Cancer (publishedVersion)
PubMed (publishedVersion)
Funders: Japan Society for the Promotion of Science (21390110)
Topics: Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
Keywords: HER2 mutation, ErbB2/Neu, lung adenocarcinoma, prognostic factors, predictive biomarkers, TP53 mutation, EGFR mutation, adenosquamous carcinoma, non-smokers, platinum resistance, EGFR tyrosine kinase inhibitors, trastuzumab, vinorelbine, gefitinib, HER2-targeted therapy, overall survival
MeSH terms: Trastuzumab, Adenocarcinoma, Adult, Aged, Aged, 80 and over, Antineoplastic Agents, DNA Mutational Analysis, Female, Humans, Japan, Lung Neoplasms, Male, Middle Aged, Mutation, Predictive Value of Tests, Prognosis, Sex Factors, Receptor, ErbB-2, Erb-b2 Receptor Tyrosine Kinases, Antibodies, Monoclonal, Humanized

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Prognostic and predictive implications of HER2/ERBB2/neu gene mutations in lung cancers

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