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Development of liquid biopsy method for breast cancer clinical application.

Research Project

Project/Area Number 17K16511
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field General surgery
Research InstitutionKumamoto University

Principal Investigator

Takashi Takeshita  熊本大学, 医学部附属病院, 助教 (60736289)

Research Collaborator Iwase Hirotaka  
Project Period (FY) 2017-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Keywordsliquid biopsy / metastatic breast cancer / ESR1 / PIK3CA / HER2 / ddPCR / Liquid biopsy / 再発乳癌 / cell-free DNA / ER陽性乳癌 / 内分泌抵抗性 / cell-free DNA / ESR1 mutation / PIK3CA mutation / biomarker / 癌
Outline of Final Research Achievements

In order to treat ER-positive advanced / recurrent breast cancer patients more effectively with endocrine therapy, elucidation of genotypes involved in endocrine therapy resistance has attracted attention. Here, as a development of the liquid biopsy method, we performed genetic analysis (ESR1, PIK3CA, AKT1, HER2) of blood samples of patients with ER positive metastatic / recurrence stocked in our department using Digital PCR. The ESR1 and PIK3CA mutations were found to be useful as therapeutic effect prediction and therapeutic effect monitoring tools. In addition, it has been reported that the HER2 mutation may contribute to endocrine therapy resistance, and we are also examining its clinical significance.

Academic Significance and Societal Importance of the Research Achievements

腫瘍組織生検に加えて、非浸襲的で連続的に患者の遺伝子情報を取得できるLiquid biopsy(血液、尿など)の臨床応用が検討され、肺がんでは既に実用化されている。乳癌でもLiquid biopsyの臨床応用へ向けて、臨床試験が組まれ、その有用性が明らかとなってきている。今回我々は内分泌療法耐性に関わる遺伝子達に注目し、ER陽性進行、再発乳癌において、ESR1変異およびPIK3CA変異が治療効果を予測するのに有用な因子であることを明らかにした。今後これらの遺伝子変異を計測するにより、対象者により効果的な治療を提供することができる可能性を示した。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (13 results)

All 2019 2018 2017

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Open Access: 4 results) Presentation (7 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results)

  • [Journal Article] dPCR Mutational Analyses in Cell-Free DNA: A Comparison with Tissues2019

    • Author(s)
      Takeshita Takashi、Iwase Hirotaka
    • Journal Title

      Methods in molecular biology (Clifton, N.J.)

      Volume: 1909 Pages: 105-118

    • DOI

      10.1007/978-1-4939-8973-7_8

    • ISBN
      9781493989720, 9781493989737
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinical significance of plasma cell-free DNA mutations in PIK3CA, AKT1, and ESR1 gene according to treatment lines in ER-positive breast cancer2018

    • Author(s)
      Takeshita Takashi、Yamamoto Yutaka、Yamamoto-Ibusuki Mutsuko、Tomiguchi Mai、Sueta Aiko、Murakami Keiichi、Iwase Hirotaka
    • Journal Title

      Molecular Cancer

      Volume: 17 Issue: 1 Pages: 67-72

    • DOI

      10.1186/s12943-018-0808-y

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] ESR1 and PIK3CA mutational status in serum and plasma from metastatic breast cancer patients: A comparative study2018

    • Author(s)
      Takeshita Takashi、Yamamoto Yutaka、Yamamoto-Ibusuki Mutsuko、Tomiguchi Mai、Sueta Aiko、Iwase Hirotaka
    • Journal Title

      Cancer Biomarkers

      Volume: 22 Issue: 2 Pages: 345-350

    • DOI

      10.3233/cbm-171161

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prevalence of ESR1 E380Q mutation in tumor tissue and plasma from Japanese breast cancer patients2017

    • Author(s)
      Takeshita Takashi、Yamamoto Yutaka、Yamamoto-Ibusuki Mutsuko、Sueta Aiko、Tomiguchi Mai、Murakami Keiichi、Omoto Yoko、Iwase Hirotaka
    • Journal Title

      BMC Cancer

      Volume: 17 Issue: 1 Pages: 786-794

    • DOI

      10.1186/s12885-017-3779-2

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Analysis of <i>ESR1</i> and <i>PIK3CA</i> mutations in plasma cell-free DNA from ER-positive breast cancer patients2017

    • Author(s)
      Takeshita Takashi、Yamamoto Yutaka、Yamamoto-Ibusuki Mutsuko、Tomiguchi Mai、Sueta Aiko、Murakami Keiichi、Omoto Yoko、Iwase Hirotaka
    • Journal Title

      Oncotarget

      Volume: 8 Issue: 32 Pages: 52142-52155

    • DOI

      10.18632/oncotarget.18479

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comparison of ESR1 Mutations in Tumor Tissue and Matched Plasma Samples from Metastatic Breast Cancer Patients2017

    • Author(s)
      Takeshita Takashi、Yamamoto Yutaka、Yamamoto-Ibusuki Mutsuko、Tomiguchi Mai、Sueta Aiko、Murakami Keiichi、Omoto Yoko、Iwase Hirotaka
    • Journal Title

      Translational Oncology

      Volume: 10 Issue: 5 Pages: 766-771

    • DOI

      10.1016/j.tranon.2017.07.004

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Clinical significance of plasma cell-free DNA mutations in PIK3CA, AKT1, and ESR1 gene according to treatment lines in ER-positive breast cancer patients.2018

    • Author(s)
      Takashi Takeshita, Mai Tomiguchi, Aiko Sueta, Mutsuko Yamamoto-Ibusuki, Yutaka Yamamoto, Hirotaka Iwase.
    • Organizer
      AACR Annual Meeting 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ER陽性乳癌における治療ライン毎のcell-free DNA PIK3CA およびESR1突然変異の臨床学的意義2018

    • Author(s)
      竹下卓志、冨口麻衣、末田愛子、藤木義敬、後藤理沙、指宿睦子、山本豊、岩瀬弘敬
    • Organizer
      第118回日本外科学会定期学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] リキッドバイオプシイ: ctDNA, CTC, microRNAなど ER陽性乳癌血漿cell-free DNA中 PIK3CA 、AKT1 、ESR1 mutationの治療ライン毎の臨床学的意義2018

    • Author(s)
      竹下卓志、藤木義敬、冨口麻衣、末田愛子、後藤理沙、指宿睦子、山本豊、岩瀬弘敬
    • Organizer
      第26回日本乳癌学会学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ER陽性乳癌患者におけるESR1 mutationのスポットおよび連続検索の臨床学的意義2017

    • Author(s)
      竹下 卓志, 冨口 麻衣, 末田 愛子, 藤木 義敬, 指宿 睦子, 山本 豊, 岩瀬 弘敬
    • Organizer
      第76回日本癌学会総会記事
    • Related Report
      2017 Research-status Report
  • [Presentation] ER陽性乳癌におけるDroplet Digital PCRを用いたcell‐free DNA内のESR1遺伝子変異のMultiplex検出2017

    • Author(s)
      竹下卓志, 冨口麻衣, 末田愛子, 西村純子, 指宿睦子, 山本豊, 岩瀬弘敬
    • Organizer
      第117回日本外科学会定期学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] ER陽性転移・再発乳癌におけるESR1およびPIK3CA体細胞突然変異の臨床的意義に関する研究2017

    • Author(s)
      竹下卓志, 冨口麻衣, 末田愛子, 藤木義敬, 後藤理沙, 邱什, 西村純子, 指宿睦子, 山本豊, 岩瀬弘敬
    • Organizer
      第25回日本乳癌学会学術総会
    • Related Report
      2017 Research-status Report
  • [Presentation] Incidence and clinical relevance of ESR1 mutations in estrogen receptor positive breast cancer patients2017

    • Author(s)
      Takashi Takeshita, Mai Tomiguchi, Aiko Sueta, Keiichi Murakami, Mutsuko Yamamoto-Ibusuki, Yutaka Yamamoto, Hirotaka Iwase
    • Organizer
      第15回日本臨床腫瘍学会学術集会
    • Related Report
      2017 Research-status Report
    • Invited

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Published: 2017-04-28   Modified: 2020-03-30  

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