The DOI matches its Crossref record; 32 of the 33 references it cites were found in a registry or an index.
Prognostic and predictive implications of HER2/ERBB2/neu gene mutations in lung cancers
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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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]
Citations
Cites
Slamon, D. J., Leyland-Jones, B., Shak, S., Fuchs, H., Paton, V., Bajamonde, A., Fleming, T., Eiermann, W., Wolter, J., Pegram, M., et al. (2001) · New England Journal of Medicine · doi:10.1056/nejm200103153441101 · Cited by 11,500
Bang, Y.-J., Van Cutsem, E., Feyereislova, A., Chung, H. C., Shen, L., Sawaki, A., Lordick, F., Ohtsu, A., Omuro, Y., Satoh, T., et al. (2010) · The Lancet · doi:10.1016/s0140-6736(10)61121-x · Cited by 7,302
Studies of the HER-2/ neu Proto-Oncogene in Human Breast and Ovarian Cancer
Slamon, D. J., Godolphin, W. J., Jones, L. A., Holt, J. A., Wong, S., Keith, D. E., Levin, W. J., Stuart, S. G., Udove, J. A., Ullrich, A., et al. (1989) · Science · doi:10.1126/science.2470152 · Cited by 6,817
Somatic mutations affect key pathways in lung adenocarcinoma
Ding, L., Getz, G., Wheeler, D. A., Mardis, E. R., McLellan, M. D., Cibulskis, K., Sougnez, C., Greulich, H., Muzny, D. M., Morgan, M. B., et al. (2008) · Nature · doi:10.1038/nature07423 · Cited by 2,681
Lamon, D. E. J. S., Eyland, B. R. L., Hak, S. T. S., Uchs, H. A. F., Aton, V. I. P., Ajamonde, A. L. B., LeMing, T., Iermann, W. O. E., Olter, J. A. W., Egram, M. A. P., et al. (2009) · Cited by 1,199
Intragenic ERBB2 kinase mutations in tumours
Stephens, P., Hunter, C., Bignell, G., Edkins, S., Davies, H., Teague, J., Stevens, C., O'Meara, S., Smith, R., Parker, A., et al. (2004) · Nature · doi:10.1038/431525b · Cited by 802 · cited 5×
“These trends were similar to the summary including 13 previous studies (Table 3) [6,7,15,20,22–30].”
BackgroundResultInfluentialSomatic Mutations of the HER2 Kinase Domain in Lung Adenocarcinomas
Shigematsu, H., Takahashi, T., Nomura, M., Majmudar, K., Suzuki, M., Lee, H., Wistuba, I. I., Fong, K. M., Toyooka, S., Shimizu, N., et al. (2005) · Cancer Research · doi:10.1158/0008-5472.can-04-4235 · Cited by 678
Self-citationWang, S. E., Narasanna, A., Pérez-Torres, M., Xiang, B., Wu, F. Y., Yang, S., Carpenter, G. F., Gazdar, A. F., Muthuswamy, S. K., & Arteaga, C. L. (2006) · Cancer Cell · doi:10.1016/j.ccr.2006.05.023 · Cited by 479
Somatic Mutations of the Protein Kinase Gene Family in Human Lung Cancer
Davies, H. R., Hunter, C., Smith, R., Stephens, P., Greenman, C., Bignell, G. R., Teague, J. W., Butler, A. P., Edkins, S., Stevens, C., et al. (2005) · Cancer Research · doi:10.1158/0008-5472.can-05-1855 · Cited by 464
Gatzemeier, U., Groth, G., Butts, C. A., van Zandwijk, N., Shepherd, F. A., Ardizzoni, A., Barton, C. M., Ghahramani, P., & Hirsh, V. (2003) · Annals of Oncology · doi:10.1093/annonc/mdh031 · Cited by 388
Flagged first, then by citations
1 of the 33 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Items 101–151 of 151
Gao, Y., Zheng, A.-H., Zhu, X., Song, J., & Xue, Q. (2018) · OncoTargets and Therapy · doi:10.2147/ott.s182812 · Cited by 8
Tomizawa, K., Ito, S., Suda, K., Fukui, T., Usami, N., Hatooka, S., Kuwano, H., Yatabe, Y., & Mitsudomi, T. (2012) · Lung Cancer · doi:10.1016/j.lungcan.2012.12.011 · Cited by 8
“[4] Tomizawa K, Suda K, Onozato R, Kosaka T, Endoh H, Sekido Y, et al.”
BackgroundNon-amplification genetic alterations of HER2 gene in non-small cell lung carcinoma
Mehta, A., Nathany, S., Tripathi, R., Sharma, S. K., Saifi, M., & Batra, U. (2020) · Journal of Clinical Pathology · doi:10.1136/jclinpath-2020-206730 · Cited by 8
Jia, Z., Xing, J., Li, J., Wang, W., Wang, Y., Song, Y., Yang, X., Xue, J., Ye, J., Li, B., et al. (2021) · Translational Lung Cancer Research · doi:10.21037/tlcr-21-107 · Cited by 7
Bispecific antibody for lung cancer: mechanisms and clinical insights
Chen, W., Zhou, A., & Zhou, Y. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1572802 · Cited by 7
Accordino, G., Lettieri, S., Bortolotto, C., Benvenuti, S., Gallotti, A., Gattoni, E., Agustoni, F., Pozzi, E., Rinaldi, P., Primiceri, C., et al. (2020) · Cancers · doi:10.3390/cancers12082105 · Cited by 7
“HER2 is activated most frequently by increased gene copy number, whereas somatic mutations rarely occur [75].”
BackgroundMetastatic HER2-amplified non-small-cell lung cancer treated with trastuzumab deruxtecan
Yun, K. M., & Bazhenova, L. A. (2023) · BMJ Case Reports · doi:10.1136/bcr-2022-253260 · Cited by 7
Molecular Histopathology and Cytopathology
Kara, A., Gelen, V., & Kara, H. (2023) · IntechOpen eBooks · doi:10.5772/intechopen.105300 · Cited by 5
Perspective Chapter: Molecular Pathology of Lung Cancer
Gandhi, S. J., Gupta, I., Menia, R., & Kumar, R. (2023) · IntechOpen eBooks · doi:10.5772/intechopen.109598 · Cited by 7
Nouvelles cibles et nouvelles molécules en oncologie thoracique
Rouvière, D., Bousquet, E., Tostivint, E. P., Milia, J., Guibert, N. M., & Mazières, J. (2015) · Revue des Maladies Respiratoires · doi:10.1016/j.rmr.2015.02.091 · Cited by 5
HER2 alterations in non-small-cell lung cancer – Druggable or undruggable?
Bondili, S. K., Nandhana, R., Noronha, V., Pawar, S., Menon, N. S., Shetty, O. A., Chougule, A., Mahajan, A., Kumar, R., Patil, V. M., et al. (2021) · Cancer Research Statistics and Treatment · doi:10.4103/crst.crst_81_21 · Cited by 5
Yamamoto, T. S., Saito, M., Kumazawa, K., Doi, A., Matsui, A., Takebe, S., Amari, T., Oyama, M., & Semb, K. A. (2011) · InTech eBooks · doi:10.5772/21965 · Cited by 4
Ou, S. I. (2014) · Postgraduate Medical Journal · doi:10.1136/postgradmedj-2012-201296rep · Cited by 5
Infrequent ERBB2 mutations in Chinese patients with non-small cell lung cancer.
Feng, S., Ling, H., Guo, H., Tong, L., Hu, G., Liao, L., Lv, X., Tan, H., & Wu, Y. (2014) · Europe PMC (PubMed Central) · doi:10.3978/j.issn.2072-1439.2014.03.20 · Cited by 4
“As with EGFR mutations, ERBB2 mutations, which may be a therapeutic target in lung cancer patients (13), are more common in Asians, adenocarcinomas, females, and never-smokers (4,5,14).”
BackgroundMetro, G., Giglio, A. D., Ricciuti, B., Siringo, M., Marinelli, D., Gelibter, A. J., Pecci, F., Berardi, R., Cantini, L., Federico, A. D., et al. (2022) · Drugs in Context · doi:10.7573/dic.2022-3-9 · Cited by 4
Long-read sequencing reveals novel transcript diversity in Polypterus senegalus
Shin, J. W., Kim, B., Lee, S. H., Kim, J., & Rhee, J. (2025) · Animal Cells and Systems · doi:10.1080/19768354.2025.2479057 · Cited by 3
“FAM13A , ERBB2 , and TCF7 are associated with lung function and various pulmonary diseases in mammals (Sasaki et al. 2006; Tomizawa et al. 2011; Zhu et al. 2015; Chuang et al. 2017; Eisenhut et al. 2017; Chen et al. 2023).”
Sakata, S., Sakamoto, Y., Takaki, A., Ishizuka, S., Saeki, S., & Fujii, K. (2018) · Internal Medicine · doi:10.2169/internalmedicine.9612-17 · Cited by 3
“reported that HER2 mutations were not associated with the prognosis of non-small-cell lung cancer patients, suggesting a negative prognostic role for the co-existence of a TP53 mutation (9).”
BackgroundWang, X., Wang, J., Chu, Y., & Hao, J. (2023) · Journal of Cancer Research and Therapeutics · doi:10.4103/jcrt.jcrt_1268_23 · Cited by 3
Ni, C., Zhang, L., Yu, X., Pang, Y., & Xu, J. (2024) · Frontiers in Oncology · doi:10.3389/fonc.2024.1440379 · Cited by 3
Ichimata, M., Kagawa, Y., Toshima, A., Igase, M., & Mizuno, T. (2025) · Veterinary and Comparative Oncology · doi:10.1111/vco.70020 · Cited by 2
Yang, G., Tian, L., & Wang, Y. (2025) · Discover Oncology · doi:10.1007/s12672-025-01749-3 · Cited by 2
Kuang, X., Xiao, J., Dai, L., Zhang, L., & He, B. (2019) · Translational Cancer Research · doi:10.21037/tcr.2019.04.10 · Cited by 2
“found that HER2 mutations are more common in women, non-smokers, and ADC (40).”
BackgroundFernández-Jardón, C. M., González‐Loureiro, M., & Castelo, J. P. (2016) · Revista Internacional de Sociología · doi:10.3989/ris.2016.74.2.035 · Cited by 2
Biochemical Pathways in Cancer
Breuer, E.-K. Y., Murph, M. M., & Craven, R. J. (2012) · Biochemistry Research International · doi:10.1155/2012/268504 · Cited by 1
Ruan, M., Chang, C., Sun, J., Liu, L., Wang, L., Lei, B., Yan, H., Zhang, H., Xie, W., & Wang, Y. (2023) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-023-05218-8 · Cited by 1
“Previous studies have shown shorter overall survival was observed in HER2 positive patients compared with HER2 negative patients in nonselected NSCLC patients (Tomizawa et al. 2011; Song et al. 2016; Wei et al. 2020).”
ResultYap, N. Y., Perumal, K., & Rajadurai, P. (2024) · ecancermedicalscience · doi:10.3332/ecancer.2024.1734 · Cited by 1
Zhang, K., & Wang, H. (2015) · Europe PMC (PubMed Central) · doi:10.3779/j.issn.1009-3419.2015.10.08 · Cited by 1
Épidémiologie du cancer bronchique : des considérations générales à l’aspect moléculaire
Mazières, J. (2014) · Revue des Maladies Respiratoires Actualités · doi:10.1016/s1877-1203(14)70583-x · Cited by 1
Molecular and Biological Basis of Lung Cancer-Part I
Chrysanthakopoulos, N. A. (2020) · doi:10.47733/gjccr.2020.1203 · Cited by 1
“HER2 genetic aberrations have been identified mainly in LADC cases (Shigematsu et al., 2005; Tomizawa et al., 2011; Cancer Genome Atlas Research Network, 2012) and mutations in tumors which consist the wild-type for EGFR and KRAS (Shigematsu et al.”
BackgroundInfluentialLi, Y., Wu, X., Fang, J., Zhao, Q., Huang, Y., & Jiang, L. (2022) · Nuclear Medicine Communications · doi:10.1097/mnm.0000000000001530 · Cited by 1
Cretella, D. (2015) · DSpaceUnipr (University of Parma)
Strategies in Patients with Other Molecular Alterations
D’Arcangelo, M., & Hirsch, F. R. (2014) · Springer eBooks · doi:10.1007/978-3-319-06062-0_12
Les mutations de HER2 dans les cancers bronchiques : caractéristiques et perspectives thérapeutiques
Mazières, J., & Milia, J. (2012) · Revue des Maladies Respiratoires Actualités · doi:10.1016/s1877-1203(12)70318-x
Pécuchet, N., Bigot, F., Henni, M., & Fabre, E. (2014) · Revue de Pneumologie Clinique · doi:10.1016/j.pneumo.2013.12.005 · Cited by 1
No Target Left Behind: Improving Therapeutic Options for ERBB2 -Mutant Non–Small Cell Lung Cancer
Redig, A. J., & Janne, P. A. (2016) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2016.04.009
Genetic Testing in Lung Cancer Treatment
Shimizu, T. (2016) · Haigan · doi:10.2482/haigan.56.242
Ebi, H., & Mitsudomi, T. (2012) · Informa Healthcare eBooks · doi:10.3109/9781841848679.005
La génétique somatique des tumeurs solides, un incontournable à l’ère de la médecine de précision
Lehmann‐Che, J., Poirot, B., Boyer, J. C., & Evrard, A. (2017) · Therapies · doi:10.1016/j.therap.2016.09.009
Chudnovsky, Y., Kumar, R. D., Schrock, A. B., Connelly, C. F., Gowen, K. A., Frampton, G. M., Erlich, R., Stephens, P. J., Miller, V. A., Ross, J. S., et al. (2017) · JCO Precision Oncology · doi:10.1200/po.16.00037
The many facets of lung adenocarcinoma – a disease comprising distinct molecular subgroups.
Gleinig, A., Huth, S., Dahmen, U., & Dirsch, O. (2015) · Medical Research Archives · doi:10.18103/mra.v1i6.411
“Two of them found no difference in overall survival (Arcila et al., 2012; Tomizawa et al., 2011), while the third reported reduced overall survival for patients with HER2 insertion mutations (Suzuki et al., 2015).”
BackgroundLung cancer and genitourinary cancers
Schrijvers, D. L. A. L. (2013) · doi:10.2217/ebo.13.211
Understanding the Molecular Kinetics in NSCLC Through Computational Method
Nimsarkar, P., Gulhane, P., & Singh, S. (2022) · Springer eBooks · doi:10.1007/978-981-19-1953-4_7
Xu, J., Ni, C., Zhang, L., Yu, X., & Pang, Y. (2023) · Research Square · doi:10.21203/rs.3.rs-2841312/v1
Hájková, N., Pavlíčková, K., Dvořák, J., Hojny, J., Krkavcová, E., Waldauf, P., Dundr, P., Drösslerová, M., Švajdler, M., Fabián, P., et al. (2025) · Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin · doi:10.1007/s00428-025-04285-1
Nanotechnology for combating chemoresistance in peripheral cancers
DCruz, C. E. M., Dhiman, A., Karmakar, A., Shirodkar, R. K., & Kumar, L. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-33343-9.00005-3
Advances in Lung Cancer Management: Novel Approaches and the Road Ahead
Choudhary, F., Mustafa, M., Farooqui, M. R., Nizam, A., Abdin, M. Z., & Farooqi, H. (2026) · Clinical Cancer Drugs · doi:10.2174/012212697x412648260114111222
Elantably, D., Meerzaman, I., Hou, A. Y., Abdelhakeem, A., & Lou, Y. (2026) · Cancers · doi:10.3390/cancers18132121
Molecular Testing in Pulmonary Tumors
Tanguay, J., Karimi, S., Hwang, D. M., & Tsao, M. (2014) · Springer eBooks · doi:10.1007/978-1-4899-8050-2_13
Metadata
- 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
- Venue
- Lung Cancer
- Publisher
- Elsevier BV
- Published
- 2011-10
- Volume
- 74
- Issue
- 1
- Pages
- 139-144
- ISSN
- 0169-5002 (ISSN-L)
- 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
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
