Masayuki Nagahashi1, YiWei Ling2, Tetsu Hayashida3, Yuko Kitagawa3, Manabu Futamura4, Kazuhiro Yoshida4, Takashi Kuwayama5, Seigo Nakamura5, Chie Toshikawa1,6, Hideko Yamauchi6, Teruo Yamauchi7, Koji Kaneko8, Chizuko Kanbayashi8, Nobuaki Sato8, Yasuo Miyoshi9, Junko Tsuchida1, Masato Nakajima1, Yoshifumi Shimada1, Hiroshi Ichikawa1, Stephen Lyle10, Kazuaki Takabe1,11,12,13,14, Shujiro Okuda2, Toshifumi Wakai1. 1. Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata City, Niigata 951-8510, Japan. 2. Division of Bioinformatics, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata City, Niigata 951-8510, Japan. 3. Department of Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjyuku-ku, Tokyo, 160-8582, Japan. 4. Department of Surgical Oncology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan. 5. Division of Breast Surgical Oncology, Department of Surgery, Showa University School of Medicine, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo 142-8666, Japan. 6. Department of Breast Surgical Oncology, Department of Internal Medicine, St. Luke's International Hospital, 9-1 Akashicho, Chuo, Tokyo 104-8560, Japan. 7. Division of Medical Oncology, Department of Internal Medicine, St. Luke's International Hospital, 9-1 Akashicho, Chuo, Tokyo 104-8560, Japan. 8. Department of Breast Oncology, Niigata Cancer Center Hospital, 15-3 Kawagishi-cho 2-Chome, Chuo-ku, Niigata City, Niigata 951-8566, Japan. 9. Department of Surgery, Division of Breast and Endocrine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan. 10. University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, Massachusetts 01655, USA. 11. Breast Surgery, Roswell Park Comprehensive Cancer Center, Elm & Carlton Streets, Buffalo, New York 14263, USA. 12. Department of Surgery, University at Buffalo Jacobs School of Medicine and Biosciences, the State University of New York, USA. 13. Department of Breast Surgery and Oncology, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402, Japan. 14. Department of Surgery, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
Abstract
PURPOSE: It has been suggested that the biological characteristics of breast cancer may differ among different geographic or ethnic populations. Indeed, triple-negative breast cancer (TNBC), the most lethal breast cancer subgroup, has been reported to show a higher incidence in Japan than in the US. However, most genomic studies of these tumors are from Western countries and the genomic landscape of TNBC in an Asian population has not been thoroughly investigated. Here, we sought to elucidate the geographic and ethnic diversity of breast cancer by examining actionable driver alterations in TNBC tumors from Japanese patients and comparing them with The Cancer Genome Atlas (TCGA) database, which gather data primarily from non-Asian patients. MATERIALS AND METHODS: We performed comprehensive genomic profiling, including an analysis of 435 known cancer genes on Japanese TNBC patients (N=53) and compared the results to independent data obtained from TCGA (N=123). RESULTS: Driver alterations were identified in 51 out of 53 Japanese patients (96%). Although the overall alteration spectrum of Japanese patients was similar to that of the TCGA, we found significant differences in the frequencies of alterations in MYC and PTK2. We identified three patients (5.7%) with a high tumor mutation burden, although no microsatellite instability was observed in any of the Japanese patients. Importantly, pathway analysis revealed that 66.0% (35/53) of Japanese patients, as well as 66.7% (82/123) of the TCGA cohort, had alterations in at least one actionable gene targetable by an FDA-approved drug. CONCLUSION: Our study identified actionable driver alterations in Japanese patients with TNBC, revealing new opportunities for targeted therapies in Asian patients.
PURPOSE: It has been suggested that the biological characteristics of breast cancer may differ among different geographic or ethnic populations. Indeed, triple-negative breast cancer (TNBC), the most lethal breast cancer subgroup, has been reported to show a higher incidence in Japan than in the US. However, most genomic studies of these tumors are from Western countries and the genomic landscape of TNBC in an Asian population has not been thoroughly investigated. Here, we sought to elucidate the geographic and ethnic diversity of breast cancer by examining actionable driver alterations in TNBC tumors from Japanese patients and comparing them with The Cancer Genome Atlas (TCGA) database, which gather data primarily from non-Asian patients. MATERIALS AND METHODS: We performed comprehensive genomic profiling, including an analysis of 435 known cancer genes on Japanese TNBC patients (N=53) and compared the results to independent data obtained from TCGA (N=123). RESULTS: Driver alterations were identified in 51 out of 53 Japanese patients (96%). Although the overall alteration spectrum of Japanese patients was similar to that of the TCGA, we found significant differences in the frequencies of alterations in MYC and PTK2. We identified three patients (5.7%) with a high tumor mutation burden, although no microsatellite instability was observed in any of the Japanese patients. Importantly, pathway analysis revealed that 66.0% (35/53) of Japanese patients, as well as 66.7% (82/123) of the TCGA cohort, had alterations in at least one actionable gene targetable by an FDA-approved drug. CONCLUSION: Our study identified actionable driver alterations in Japanese patients with TNBC, revealing new opportunities for targeted therapies in Asian patients.
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