Yumi Endo1, Yu Dong1, Nobuyasu Yoshimoto1, Tomoko Asano1, Yukari Hato1, Hiroko Yamashita2, Shinya Sato3, Satoru Takahashi3, Yoshitaka Fujii1, Tatsuya Toyama4. 1. Department of Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya. 2. Department of Breast and Endocrine Surgery, Hokkaido University Hospital, Sapporo. 3. Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. 4. Department of Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya t.toyama@med.nagoya-cu.ac.jp.
Abstract
OBJECTIVE: Human epidermal growth factor receptor 2 (HER2) gene amplification is a major therapeutic target in breast cancer, and has been introduced as a predictive biomarker to identify patients who may benefit from therapy with anti-human epidermal growth factor receptor 2 agents. Human epidermal growth factor receptor 2 somatic mutations have been reported in patients without human epidermal growth factor receptor 2 gene amplification. Since these are activating mutations, these patients may also benefit from human epidermal growth factor receptor 2-targeted drugs. METHODS: In this study, we searched for human epidermal growth factor receptor 2 mutations in a group of 286 Japanese breast cancer patients with human epidermal growth factor receptor 2-negative tumors. The activating mutations of human epidermal growth factor receptor 2 identified were analyzed by direct Sanger sequencing of two major areas: the extracellular domain at 309-310 and the kinase domain between 755 and 781. RESULTS: Two tumors were found to have a human epidermal growth factor receptor 2 somatic mutation; one with I767M mutation and another with D769Y. No mutation was observed in the extracellular domain. One of these patients with human epidermal growth factor receptor 2 mutation recurred early with liver metastasis. CONCLUSIONS: Better knowledge of human epidermal growth factor receptor 2 mutation status will help us to choose personalized molecular targeted therapy for use in human epidermal growth factor receptor 2-negative Japanese breast cancer patients.
OBJECTIVE:Human epidermal growth factor receptor 2 (HER2) gene amplification is a major therapeutic target in breast cancer, and has been introduced as a predictive biomarker to identify patients who may benefit from therapy with anti-human epidermal growth factor receptor 2 agents. Human epidermal growth factor receptor 2 somatic mutations have been reported in patients without human epidermal growth factor receptor 2 gene amplification. Since these are activating mutations, these patients may also benefit from human epidermal growth factor receptor 2-targeted drugs. METHODS: In this study, we searched for human epidermal growth factor receptor 2 mutations in a group of 286 Japanese breast cancerpatients with human epidermal growth factor receptor 2-negative tumors. The activating mutations of human epidermal growth factor receptor 2 identified were analyzed by direct Sanger sequencing of two major areas: the extracellular domain at 309-310 and the kinase domain between 755 and 781. RESULTS: Two tumors were found to have a human epidermal growth factor receptor 2 somatic mutation; one with I767M mutation and another with D769Y. No mutation was observed in the extracellular domain. One of these patients with human epidermal growth factor receptor 2 mutation recurred early with liver metastasis. CONCLUSIONS: Better knowledge of human epidermal growth factor receptor 2 mutation status will help us to choose personalized molecular targeted therapy for use in human epidermal growth factor receptor 2-negative Japanese breast cancerpatients.
Authors: Gabrielle Deniziaut; Jean Christophe Tille; François-Clément Bidard; Sophie Vacher; Anne Schnitzler; Walid Chemlali; Laurence Trémoulet; Laetitia Fuhrmann; Paul Cottu; Roman Rouzier; Ivan Bièche; Anne Vincent-Salomon Journal: Oncotarget Date: 2016-11-08