Kiichiro Ninomiya1, Tae Hata2, Hiroshige Yoshioka2, Kadoaki Ohashi3, Akihiro Bessho4, Shinobu Hosokawa4, Nobuhisa Ishikawa5, Masahiro Yamasaki6, Takuo Shibayama7, Keisuke Aoe8, Toshiyuki Kozuki9, Shingo Harita10, Yutaka Ueda11, Toshi Murakami12, Nobukazu Fujimoto13, Hiroyuki Yanai14, Shinichi Toyooka15, Minoru Takata16, Katsuyuki Hotta17, Katsuyuki Kiura18. 1. Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. 2. Department of Respiratory Medicine, Kurashiki Central Hospital, Kurashiki, Japan. 3. Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan; Department of Respiratory Medicine, Okayama University Hospital, Okayama, Japan. 4. Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital, Okayama, Japan. 5. Department of Respiratory Medicine, Hiroshima Prefectural Hospital, Hiroshima, Japan. 6. Department of Respiratory Disease, Hiroshima Red Cross Hospital & Atomic Bomb Survivors Hospital, Hiroshima, Japan. 7. Department of Respiratory Medicine, National Hospital Organization Okayama Medical Center, Okayama, Japan. 8. Department of Medical Oncology, National Hospital Organization Yamaguchi-Ube Medical Center, Ube, Japan. 9. Department of Thoracic Oncology and Medicine, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan. 10. Department of Respiratory Medicine, Chugoku Central Hospital, Fukuyama, Japan; Department of Respiratory Medicine, Okayama Saiseikai General Hospital, Okayama, Japan. 11. Department of Respiratory Medicine, Kagawa Prefectural Central Hospital, Kagawa, Japan. 12. Department of Respiratory Medicine, Japanese Red Cross Society Himeji Hospital, Himeji, Japan; Department of Respiratory Medicine, Onomichi Municipal Hospital, Onomichi, Japan. 13. Department of Medical Oncology, Okayama Rosai Hospital, Okayama, Japan. 14. Department of Pathology, Okayama University Hospital, Okayama, Japan. 15. Department of General Thoracic Surgery, Okayama University Hospital, Okayama, Japan. 16. Laboratory of DNA Damage Signaling, Department of Late Effects Studies, Radiation Biology Center, Graduate School Biostudies, Kyoto University, Kyoto, Japan. 17. Department of Respiratory Medicine, Okayama University Hospital, Okayama, Japan; Center of Innovative Clinical Medicine, Okayama University Hospital, Okayama, Japan. Electronic address: khotta@okayama-u.ac.jp. 18. Department of Respiratory Medicine, Okayama University Hospital, Okayama, Japan.
Abstract
BACKGROUND: Human epidermal growth factor 2 (HER2) is a potential driver oncogene. Although HER2-targeted precision therapy has been tested in non-small cell lung cancer (NSCLC), the demographic characteristics of HER2-positive NSCLC have not been systematically defined. METHODS: Patients with pathologically confirmed stage IIIB/IV or recurrent NSCLC, Eastern Cooperative Oncology Group performance status 0 to 2, were prospectively registered. HER2 immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) assays were performed to screen patients. HER2 mutations were identified by using direct gene sequencing. The aim of this study was to clarify the frequency, characteristics, and outcome of HER2-positive NSCLC. HER2 was defined as positive if the tumor harbored IHC3+, IHC2+/FISH+, or exon 20 insertion mutations. RESULTS: Of the 1,126 tumors screened, 34 (3.0%) were IHC3+, and 34 (3.0%) were IHC2+/FISH+. Among the 724 epidermal growth factor receptor wild-type tumors, 21 (2.9%) were HER2-mutant tumors, including A775-G776insYVMA (n = 15). Interestingly, the IHC3+ tumors and mutant tumors were entirely exclusive. Female patients had HER2-mutant tumors more frequently, whereas both IHC3+ and IHC2+/FISH+ tumors were detected more often in male subjects and smokers. Patients with an HER2-aberrant tumor had a significantly worse prognosis than those with epidermal growth factor receptor-positive and anaplastic lymphoma kinase-positive tumors, possibly due to the low proportion that received HER2-targeted therapies (n = 15 [26%]) and low response rates of 0% and 14% in patients with HER2-overexpressing and HER2-mutant tumors, respectively. CONCLUSIONS: This prospective large-scale cohort study is the first to show comprehensively the frequency and clinical demographic characteristics of those with HER2-positive advanced lung tumors in detail, providing critical historical data for future drug development against HER2-positive NSCLC. Future treatment strategies would be developed stratified according to the types of HER2 aberrations. TRIAL REGISTRY: UMIN Registration No. 000017003; URL: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000019691.
BACKGROUND:Human epidermal growth factor 2 (HER2) is a potential driver oncogene. Although HER2-targeted precision therapy has been tested in non-small cell lung cancer (NSCLC), the demographic characteristics of HER2-positive NSCLC have not been systematically defined. METHODS:Patients with pathologically confirmed stage IIIB/IV or recurrent NSCLC, Eastern Cooperative Oncology Group performance status 0 to 2, were prospectively registered. HER2 immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) assays were performed to screen patients. HER2 mutations were identified by using direct gene sequencing. The aim of this study was to clarify the frequency, characteristics, and outcome of HER2-positive NSCLC. HER2 was defined as positive if the tumor harbored IHC3+, IHC2+/FISH+, or exon 20 insertion mutations. RESULTS: Of the 1,126 tumors screened, 34 (3.0%) were IHC3+, and 34 (3.0%) were IHC2+/FISH+. Among the 724 epidermal growth factor receptor wild-type tumors, 21 (2.9%) were HER2-mutant tumors, including A775-G776insYVMA (n = 15). Interestingly, the IHC3+ tumors and mutant tumors were entirely exclusive. Female patients had HER2-mutant tumors more frequently, whereas both IHC3+ and IHC2+/FISH+ tumors were detected more often in male subjects and smokers. Patients with an HER2-aberrant tumor had a significantly worse prognosis than those with epidermal growth factor receptor-positive and anaplastic lymphoma kinase-positive tumors, possibly due to the low proportion that received HER2-targeted therapies (n = 15 [26%]) and low response rates of 0% and 14% in patients with HER2-overexpressing and HER2-mutant tumors, respectively. CONCLUSIONS: This prospective large-scale cohort study is the first to show comprehensively the frequency and clinical demographic characteristics of those with HER2-positive advanced lung tumors in detail, providing critical historical data for future drug development against HER2-positive NSCLC. Future treatment strategies would be developed stratified according to the types of HER2 aberrations. TRIAL REGISTRY: UMIN Registration No. 000017003; URL: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000019691.
Authors: Anna Michelotti; Marco de Scordilli; Elisa Bertoli; Elisa De Carlo; Alessandro Del Conte; Alessandra Bearz Journal: Int J Mol Sci Date: 2022-06-17 Impact factor: 6.208
Authors: Alessandro Russo; Ana Rita Lopes; Michael G McCusker; Sandra Gimenez Garrigues; Giuseppina R Ricciardi; Katherine E Arensmeyer; Katherine A Scilla; Ranee Mehra; Christian Rolfo Journal: Curr Oncol Rep Date: 2020-04-16 Impact factor: 5.075