Therapeutic Potential of Afatinib for Cancers with ERBB2 (HER2) Transmembrane Domain Mutations G660D and V659E

Hiromasa Yamamoto, Shinichi Toyooka, Takashi Ninomiya, Shigemi Matsumoto, Masashi Kanai, Shuta Tomida, Katsuyuki Kiura, Manabu Muto, Ken Suzawa, Patrice Desmeules, Mark G. Kris, Bob T. Li, Marc Ladanyi

Research output: Contribution to journalArticle

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Abstract

We previously reported on a family with hereditary lung cancer, in which a germline mutation in the transmembrane domain (G660D) of avian erythroblastic leukemia viral oncogene homolog 2 (erb-b2 receptor tyrosine kinase 2) (ERBB2; human epidermal growth factor receptor 2 [HER2]) seemed to be responsible for the cancer predisposition. Although few data are available on treatment, anti-ERBB2 therapeutic agents may be effective for ERBB2-mutant cancers. The familial lung cancer patient in one of the authors’ institutes developed bone metastasis with enlarging lung tumors and was treated with the ERBB2 inhibitor afatinib. We also encountered a patient with ampullary adenocarcinoma with ERBB2 G660D and S310F comutations in another institute of the authors’, revealed by comprehensive genomic profiling. This patient was then treated with afatinib and also achieved transitory response. We also searched for ERBB2 transmembrane mutations in various types of cancers in PubMed, The Cancer Genome Atlas (TCGA), and the Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) database. Besides our two cases, two patients with V659E mutations were found via PubMed. Three potential patients were found in TCGA. In addition, MSK-IMPACT allowed identification of three additional urothelial carcinomas with G660D mutations and two lung adenocarcinomas with V659E mutations. Our experience suggests that establishing a database of integrated information regarding the clinical genome and therapeutic outcome of patients with recurrent but less common mutations is essential to implement precision oncology. Key Points: Rare but targetable mutations such as avian erythroblastic leukemia viral oncogene homolog 2 (erb-b2 receptor tyrosine kinase 2) (ERBB2; human epidermal growth factor receptor 2 [HER2]) transmembrane domain (TMD) mutations can be detected by comprehensive genomic profiling. Afatinib may be effective for patients with cancer with ERBB2 (HER2) TMD mutations. In order to implement precision oncology, it is important to establish a database of integrated information regarding the clinical genomes and therapeutic outcomes of patients with recurrent but less common mutations.

Original languageEnglish
Pages (from-to)150-154
Number of pages5
JournalOncologist
Volume23
Issue number2
DOIs
Publication statusPublished - Feb 1 2018

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Mutation
Neoplasms
TYK2 Kinase
Therapeutics
Genome
Atlases
Databases
Oncogenes
PubMed
Lung Neoplasms
Leukemia
BIBW 2992
human ERBB2 protein
Germ-Line Mutation
Adenocarcinoma
Neoplasm Metastasis
Carcinoma
Bone and Bones
Lung

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Therapeutic Potential of Afatinib for Cancers with ERBB2 (HER2) Transmembrane Domain Mutations G660D and V659E. / Yamamoto, Hiromasa; Toyooka, Shinichi; Ninomiya, Takashi; Matsumoto, Shigemi; Kanai, Masashi; Tomida, Shuta; Kiura, Katsuyuki; Muto, Manabu; Suzawa, Ken; Desmeules, Patrice; Kris, Mark G.; Li, Bob T.; Ladanyi, Marc.

In: Oncologist, Vol. 23, No. 2, 01.02.2018, p. 150-154.

Research output: Contribution to journalArticle

Yamamoto, Hiromasa ; Toyooka, Shinichi ; Ninomiya, Takashi ; Matsumoto, Shigemi ; Kanai, Masashi ; Tomida, Shuta ; Kiura, Katsuyuki ; Muto, Manabu ; Suzawa, Ken ; Desmeules, Patrice ; Kris, Mark G. ; Li, Bob T. ; Ladanyi, Marc. / Therapeutic Potential of Afatinib for Cancers with ERBB2 (HER2) Transmembrane Domain Mutations G660D and V659E. In: Oncologist. 2018 ; Vol. 23, No. 2. pp. 150-154.
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