Actionable gene alterations in an Asian population with triple- negative breast cancer

Masayuki Nagahashi, Yi Wei Ling, Tetsu Hayashida, Yuko Kitagawa, Manabu Futamura, Kazuhiro Yoshida, Takashi Kuwayama, Seigo Nakamura, Chie Toshikawa, Hideko Yamauchi, Teruo Yamauchi, Koji Kaneko, Chizuko Kanbayashi, Nobuaki Sato, Yasuo Miyoshi, Junko Tsuchida, Masato Nakajima, Yoshifumi Shimada, Hiroshi Ichikawa, Stephen LyleKazuaki Takabe, Shujiro Okuda, Toshifumi Wakai

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Purpose It has been suggested that the biologic 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 occur at a higher incidence in Japan than in the United States. 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 gathers data primarily from non-Asian patients. Materials and Methods We performed comprehensive genomic profiling, including an analysis of 435 known cancer genes, among Japanese patients with TNBC (n = 53) and compared the results with independent data obtained from TCGA (n = 123). Results Driver alterations were identified in 51 (96%) of 53 Japanese patients. Although the overall alteration spectrum among Japanese patients was similar to that of TCGA, we found significant differences in the frequencies of alterations in MYC and PTK2. We identified three patients (5.7%) with a high tumor mutational burden, although no microsatellite instability was observed in any of the Japanese patients. Importantly, pathway analysis revealed that 66.0% (35 of 53) of Japanese patients, as well as 66.7% (82 of 123) of TCGA cohort, had alterations in at least one actionable gene targetable by US Food and Drug Administration-approved drug. Conclusion Our study identified actionable driver alterations in Japanese patients with TNBC, revealing new opportunities for targeted therapies in Asian patients.

Original languageEnglish
JournalJCO Precision Oncology
Volume2
DOIs
Publication statusPublished - 2018 Jan 1

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Triple Negative Breast Neoplasms
Atlases
Population
Genes
Genome
Breast Neoplasms
Neoplasms
Microsatellite Instability
Neoplasm Genes
United States Food and Drug Administration
Tumor Burden
Japan
Databases

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Actionable gene alterations in an Asian population with triple- negative breast cancer. / Nagahashi, Masayuki; Ling, Yi Wei; Hayashida, Tetsu; Kitagawa, Yuko; Futamura, Manabu; Yoshida, Kazuhiro; Kuwayama, Takashi; Nakamura, Seigo; Toshikawa, Chie; Yamauchi, Hideko; Yamauchi, Teruo; Kaneko, Koji; Kanbayashi, Chizuko; Sato, Nobuaki; Miyoshi, Yasuo; Tsuchida, Junko; Nakajima, Masato; Shimada, Yoshifumi; Ichikawa, Hiroshi; Lyle, Stephen; Takabe, Kazuaki; Okuda, Shujiro; Wakai, Toshifumi.

In: JCO Precision Oncology, Vol. 2, 01.01.2018.

Research output: Contribution to journalArticle

Nagahashi, M, Ling, YW, Hayashida, T, Kitagawa, Y, Futamura, M, Yoshida, K, Kuwayama, T, Nakamura, S, Toshikawa, C, Yamauchi, H, Yamauchi, T, Kaneko, K, Kanbayashi, C, Sato, N, Miyoshi, Y, Tsuchida, J, Nakajima, M, Shimada, Y, Ichikawa, H, Lyle, S, Takabe, K, Okuda, S & Wakai, T 2018, 'Actionable gene alterations in an Asian population with triple- negative breast cancer', JCO Precision Oncology, vol. 2. https://doi.org/10.1200/PO.17.00211
Nagahashi, Masayuki ; Ling, Yi Wei ; Hayashida, Tetsu ; Kitagawa, Yuko ; Futamura, Manabu ; Yoshida, Kazuhiro ; Kuwayama, Takashi ; Nakamura, Seigo ; Toshikawa, Chie ; Yamauchi, Hideko ; Yamauchi, Teruo ; Kaneko, Koji ; Kanbayashi, Chizuko ; Sato, Nobuaki ; Miyoshi, Yasuo ; Tsuchida, Junko ; Nakajima, Masato ; Shimada, Yoshifumi ; Ichikawa, Hiroshi ; Lyle, Stephen ; Takabe, Kazuaki ; Okuda, Shujiro ; Wakai, Toshifumi. / Actionable gene alterations in an Asian population with triple- negative breast cancer. In: JCO Precision Oncology. 2018 ; Vol. 2.
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abstract = "Purpose It has been suggested that the biologic 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 occur at a higher incidence in Japan than in the United States. 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 gathers data primarily from non-Asian patients. Materials and Methods We performed comprehensive genomic profiling, including an analysis of 435 known cancer genes, among Japanese patients with TNBC (n = 53) and compared the results with independent data obtained from TCGA (n = 123). Results Driver alterations were identified in 51 (96{\%}) of 53 Japanese patients. Although the overall alteration spectrum among Japanese patients was similar to that of TCGA, we found significant differences in the frequencies of alterations in MYC and PTK2. We identified three patients (5.7{\%}) with a high tumor mutational burden, although no microsatellite instability was observed in any of the Japanese patients. Importantly, pathway analysis revealed that 66.0{\%} (35 of 53) of Japanese patients, as well as 66.7{\%} (82 of 123) of TCGA cohort, had alterations in at least one actionable gene targetable by US Food and Drug Administration-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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T1 - Actionable gene alterations in an Asian population with triple- negative breast cancer

AU - Nagahashi, Masayuki

AU - Ling, Yi Wei

AU - Hayashida, Tetsu

AU - Kitagawa, Yuko

AU - Futamura, Manabu

AU - Yoshida, Kazuhiro

AU - Kuwayama, Takashi

AU - Nakamura, Seigo

AU - Toshikawa, Chie

AU - Yamauchi, Hideko

AU - Yamauchi, Teruo

AU - Kaneko, Koji

AU - Kanbayashi, Chizuko

AU - Sato, Nobuaki

AU - Miyoshi, Yasuo

AU - Tsuchida, Junko

AU - Nakajima, Masato

AU - Shimada, Yoshifumi

AU - Ichikawa, Hiroshi

AU - Lyle, Stephen

AU - Takabe, Kazuaki

AU - Okuda, Shujiro

AU - Wakai, Toshifumi

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Purpose It has been suggested that the biologic 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 occur at a higher incidence in Japan than in the United States. 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 gathers data primarily from non-Asian patients. Materials and Methods We performed comprehensive genomic profiling, including an analysis of 435 known cancer genes, among Japanese patients with TNBC (n = 53) and compared the results with independent data obtained from TCGA (n = 123). Results Driver alterations were identified in 51 (96%) of 53 Japanese patients. Although the overall alteration spectrum among Japanese patients was similar to that of TCGA, we found significant differences in the frequencies of alterations in MYC and PTK2. We identified three patients (5.7%) with a high tumor mutational burden, although no microsatellite instability was observed in any of the Japanese patients. Importantly, pathway analysis revealed that 66.0% (35 of 53) of Japanese patients, as well as 66.7% (82 of 123) of TCGA cohort, had alterations in at least one actionable gene targetable by US Food and Drug Administration-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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