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Clarification of the molecular mechanism of Japanese triple negative breast cancers and the development of innovative therapy for them

Research Project

Project/Area Number 20591549
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General surgery
Research InstitutionKyushu University

Principal Investigator

TOKUNAGA Eriko  Kyushu University, 大学病院, 学術研究員 (50325453)

Co-Investigator(Kenkyū-buntansha) SHIOTANI Satoko  九州大学, 大学病院, 医員 (90419549)
OKI Eiji  九州大学, 医学研究院, 非常勤講師 (70380392)
SADANAGA Noriaki  九州大学, 医学研究院, 非常勤講師 (20304826)
OKADA Satoko  九州大学, 大学病院, 医員 (50546562)
AKIYOSHI Sayuri  九州大学, 大学病院, 医員 (50567360)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2010: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2008: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords乳癌 / トリプルネガティブ / basal-like / BRCA / FA経路 / cancer stem cell / triple negative (TN)乳癌 / BRCA1 / 染色体不安定性 / LOH / FANCJ / triple negative(TN)乳癌 / 悪性度 / サブタイプ / triple negative乳癌 / FANCF / 治療標的
Research Abstract

The lack of efficient treatment for triple negative breast cancers (TNBCs) results in their poor prognosis, and it is necessary to clarify the biological features and molecular mechanism of TNBCs in order to develop new efficient strategies. In this study, we investigated the relationships between TNBCs and abnormalities in BRCA/fanconi anemia (FA) pathway. The incidence and frequency of LOH was significantly higher in TN groups, and the incidence and frequency of LOH was increased as the nuclear grade was elevated. In the tumors with BRCA1 LOH, the incidence of LOH at tumor suppressor genes such as BRCA2, TP53, PTENwas higher and they were genetically unstable. The prognosis of the patients with tumors with BRCA1 LOH was significantly poor. There is a close correlation between TNBCs and abnormalities in BRCA/ FA pathway, and this pathway is considered important therapeutic targets for TNBCs.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (42 results)

All 2011 2010 2009 2008 Other

All Journal Article (16 results) (of which Peer Reviewed: 12 results) Presentation (26 results)

  • [Journal Article] Low incidence of methylation of the promoter region of the FANCF gene in Japanese primary breast cancer.2011

    • Author(s)
      Tokunaga E, Okada S, Kitao H, Shiotani S, Saeki H, Endo K, Morita M, Kakeji Y, Maehara Y
    • Journal Title

      Breast Cancer. 18(2)

    • NAID

      10029407629

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] 乳癌のintrinsic subtypeと治療感受性2010

    • Author(s)
      徳永えり子、秋吉清百合、山下奈真、岡田敏子、前原喜彦
    • Journal Title

      最新医学 65

      Pages: 1275-1289

    • Related Report
      2010 Final Research Report
  • [Journal Article] HB-EGF orchestrates the complex signals involved in triple-negative and trastuzumab-resistant breast cancer.2010

    • Author(s)
      Yotsumoto F, Oki E, Tokunaga E, et al
    • Journal Title

      Int J Cancer

      Volume: 127 Pages: 2707-17

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Predictive factors for anthracycline-based chemotherapy for human breast cancer.2010

    • Author(s)
      Miyoshi Y, Tokunaga E, et al
    • Journal Title

      Breast Cancer

      Volume: 17 Pages: 103-109

    • NAID

      10027255423

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 乳癌のintrinsic subtypeと治療感受性2010

    • Author(s)
      徳永えり子, 他
    • Journal Title

      最新医学

      Volume: 65 Pages: 1275-1289

    • Related Report
      2010 Annual Research Report
  • [Journal Article] Deregulation of the Akt pathway in human cancer.2008

    • Author(s)
      Tokunaga E, Oki E, Egashira A, Sadanaga N, Morita M, Kakeji Y, Maehara Y
    • Journal Title

      Curr Cancer Drug Targets. 8(1)

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] ファンコニ貧血とゲノム不安定性2008

    • Author(s)
      北尾洋之、藤中良彦、久保信英、中ノ子智徳、吉永敬士、徳永えり子、佐伯浩司、遠藤和也、森田勝、掛地吉弘、前原喜彦
    • Journal Title

      福岡医学雑誌 99(6)

    • NAID

      120000981513

    • Related Report
      2010 Final Research Report
  • [Journal Article] Deregulation of the Akt pathway in human cancer.2008

    • Author(s)
      Tokunaga E, et al
    • Journal Title

      Current Cancer Drug Targets 8

      Pages: 27-36

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Low nuclear grade but not cell proliferation predictive of pathological complete response to docetaxel in human breast cancers.2008

    • Author(s)
      Miyoshi Y, Tokunaga E, et al
    • Journal Title

      J Cancer Res Clin Oncol 134

      Pages: 561-7

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Topoisomerase IIalpha-positive and BRCA1-negative phenotype : association with favorable response to epirubicin-based regimens for human breast cancers.2008

    • Author(s)
      Miyoshi Y, Tokunaga E, et al
    • Journal Title

      Cancer Lett 26

      Pages: 44-53

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] High incidence and frequency of LOH are associated with aggressive features of high-grade HER2 and triple-negative breast cancers.

    • Author(s)
      徳永えり子, 岡田敏子, 山下奈真, 秋吉清百合, 北尾洋之, 森田勝, 掛地吉弘, 前原喜彦
    • Journal Title

      Breast Cancer in press.

    • NAID

      10030981059

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] BRCA変異乳癌

    • Author(s)
      徳永えり子、北尾洋之、前原喜彦
    • Journal Title

      Current Therapy 2011 29(5)

      Pages: 360-366

    • Related Report
      2010 Final Research Report
  • [Journal Article] Low incidence of methylation of the promoter region of the FANCF gene in Japanese primary breast cancer.

    • Author(s)
      Tokunaga E, et al
    • Journal Title

      Breast Cancer

      Volume: (in press)

    • NAID

      10029407629

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] High incidence and frequency of LOH are associated with aggressive features of high-grade HER2 and triple negative breast cancers.

    • Author(s)
      Tokunaga E, et al
    • Journal Title

      Breast Cancer

      Volume: (in press)

    • NAID

      10030981059

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Low incidence of methylation of the promoter region of the FANCF gene in Japanese primary breast cancer

    • Author(s)
      Tokunaga E, et al
    • Journal Title

      Breast Cancer (in press)

    • NAID

      10029407629

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Predictive factors for anthracycline-based chemotherapy for human breast cancer

    • Author(s)
      Miyoshi Y, Tokunaga E, et al
    • Journal Title

      Breast Cancer (in press)

    • NAID

      10027255423

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] Cytoplasmic MTDH overexpression promotes metastasis and chemoresistance and leads to poor prognosis in breast cancer.2010

    • Author(s)
      徳永えり子
    • Organizer
      第69回日本癌学会学術総会
    • Place of Presentation
      大阪
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] Significance of the FANCJ/BRIPI expression in Triple-Negative Breast Cancer2010

    • Author(s)
      山下奈真
    • Organizer
      22nd Annual Fanconi Anemia Research Fund Scientific Symposium
    • Place of Presentation
      ミネアポリス
    • Related Report
      2010 Final Research Report
  • [Presentation] triple negative乳癌とEMTの関連についての検討2010

    • Author(s)
      山下奈真
    • Organizer
      第48回日本癌治療学会学術総会
    • Place of Presentation
      京都
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] MTDH過剰発現と遠隔転移、抗癌剤耐性との関連:新たな分子標的としての可能性2010

    • Author(s)
      徳永えり子
    • Organizer
      第48回日本癌治療学会学術総会
    • Place of Presentation
      京都
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] Different impact of loss of heterozygosity at BRCAI and BRCA2 loci on breast cancer prognosis by the subtype approximated by estrogen receptor, progesterone receptor and HER22010

    • Author(s)
      岡田敏子
    • Organizer
      AACR/JCR joint conference
    • Place of Presentation
      Hawaii
    • Related Report
      2010 Final Research Report
  • [Presentation] 日本人乳癌症例におけるBRCA1、BRCA2のLOHに関する研究2010

    • Author(s)
      岡田敏子、徳永えり子, 他
    • Organizer
      第110回日本外科学会定期学術集会
    • Place of Presentation
      名古屋
    • Related Report
      2010 Annual Research Report
  • [Presentation] 乳癌におけるFOXO3a発現の意義2010

    • Author(s)
      藤中良彦、徳永えり子, 他
    • Organizer
      第110回日本外科学会定期学術集会
    • Place of Presentation
      名古屋
    • Related Report
      2010 Annual Research Report
  • [Presentation] 乳癌の分子サブタイプluminal AにおけるKi67の発現と予後および化学療法の必要性に関する研究2010

    • Author(s)
      久松雄一、徳永えり子, 他
    • Organizer
      第110回日本外科学会定期学術集会
    • Place of Presentation
      名古屋
    • Related Report
      2010 Annual Research Report
  • [Presentation] Expression of Forkhead-box protein A1 (FOXA1) as a significant prognostic and predictive marker for ER-positive breast cancer.2010

    • Author(s)
      Tokunaga E, Hisamatsu Y, et al
    • Organizer
      Annual Meeting of American Society of Clinical Oncology (ASCO)
    • Place of Presentation
      シカゴ
    • Related Report
      2010 Annual Research Report
  • [Presentation] Luminalタイプ乳癌におけるGATA-3/FOXA1/ERネットワークとホルモン感受性2010

    • Author(s)
      徳永えり子、久松雄一, 他
    • Organizer
      第18回日本乳癌学会学術総会
    • Place of Presentation
      札幌
    • Related Report
      2010 Annual Research Report
  • [Presentation] 乳癌におけるFOXA1の発現とホルモン療法感受性の検討2010

    • Author(s)
      久松雄一、徳永えり子, 他
    • Organizer
      第18回日本乳癌学会学術総会
    • Place of Presentation
      札幌
    • Related Report
      2010 Annual Research Report
  • [Presentation] 乳癌におけるPI3K/Akt経路の活性化とホルモン治療抵抗性とその克服2010

    • Author(s)
      徳永えり子, 他
    • Organizer
      第14回がん分子標的治療学会
    • Place of Presentation
      東京
    • Related Report
      2010 Annual Research Report
  • [Presentation] Significance of the FANCJ/BRIP1 expression in Triple-Negative Breast Cancer.2010

    • Author(s)
      Yamashita N, Tokunaga E, et al
    • Organizer
      22nd Annual Fanconi Anemia Research Fund Scientific Symposium
    • Place of Presentation
      ミネアポリス
    • Related Report
      2010 Annual Research Report
  • [Presentation] Different impact of loss of heterozygosity at BRCA1 and BRCA2 loci on breast cancer prognosis by the subtype approximated by estrogen receptor, progesterone receptor and HER22010

    • Author(s)
      岡田敏子, 徳永えり子, et al
    • Organizer
      AACR/JCR joint conference
    • Place of Presentation
      Hawaii
    • Related Report
      2009 Annual Research Report
  • [Presentation] 日本人若年者乳がんの生物学的特徴と予後規定因子の解明2009

    • Author(s)
      徳永えり子
    • Organizer
      第47回 日本癌治療学会学術集会
    • Place of Presentation
      横浜
    • Related Report
      2010 Final Research Report
  • [Presentation] 日本人乳癌におけるBRCA1, BRCA2のLOHとMolecular subtypeとの関連2009

    • Author(s)
      岡田敏子
    • Organizer
      第47回 日本癌治療学会学術集会
    • Place of Presentation
      横浜
    • Related Report
      2010 Final Research Report
  • [Presentation] 乳癌においてMTDHの活性化により遠隔転移が促進され、予後不良となる2009

    • Author(s)
      徳永えり子
    • Organizer
      第68回 日本癌学会学術総会
    • Place of Presentation
      横浜
    • Related Report
      2010 Final Research Report 2009 Annual Research Report
  • [Presentation] 日本人乳癌症例におけるBRCA1, BRCA2のLOHに関する研究2009

    • Author(s)
      岡田敏子
    • Organizer
      第17回 日本乳癌学会学術総会
    • Place of Presentation
      東京
    • Related Report
      2010 Final Research Report 2009 Annual Research Report
  • [Presentation] 日本人乳癌症例におけるBRCA1, BRCA2のLOHに関する研究2009

    • Author(s)
      岡田敏子
    • Organizer
      第109回 日本外科学会定期学術集会
    • Place of Presentation
      福岡
    • Related Report
      2010 Final Research Report 2009 Annual Research Report
  • [Presentation] 日本人乳癌におけるBRCA1, BRCA2のLOHと Molecular subtype との関連2009

    • Author(s)
      岡田敏子, 徳永えり子, 他
    • Organizer
      第47回 日本癌治療学会学術集会
    • Place of Presentation
      横浜
    • Related Report
      2009 Annual Research Report
  • [Presentation] 日本人若年者乳がんの生物学的特徴と予後基底因子の解明2009

    • Author(s)
      徳永えり子, 他
    • Organizer
      第47回 日本癌治療学会学術集会
    • Place of Presentation
      横浜
    • Related Report
      2009 Annual Research Report
  • [Presentation] トリプルネガティブ乳癌における染色体不安定性と抗癌剤の選択2008

    • Author(s)
      徳永えり子
    • Organizer
      第46回日本癌治療学会総会
    • Place of Presentation
      名古屋
    • Related Report
      2010 Final Research Report 2008 Annual Research Report
  • [Presentation] トリプルネガティブ及びand HER2過剰発現乳癌における高頻度LOHと高悪性度との関連2008

    • Author(s)
      徳永えり子
    • Organizer
      第67回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Related Report
      2010 Final Research Report 2008 Annual Research Report
  • [Presentation] トリプルネガティブ乳癌における染色体不安定性2008

    • Author(s)
      徳永えり子
    • Organizer
      第16回日本乳癌学会学術総会
    • Place of Presentation
      大阪
    • Related Report
      2010 Final Research Report 2008 Annual Research Report
  • [Presentation] Basal type breast cancers are most genetically unstable among breast cancer subtypes approximated by estrogen receptor, progesterone receptor and HER2.2008

    • Author(s)
      徳永えり子, et al.
    • Organizer
      The 26th Congress of the International Association for Breast Cancer Research.
    • Place of Presentation
      Kurashiki, Japan
    • Related Report
      2010 Final Research Report
  • [Presentation] Basal type breast cancers are most genetically unstable among breast cancer subtypes approximated by estrogen receptor, progesterone receptor and HER22008

    • Author(s)
      Tokunaga E, et al
    • Organizer
      The 26th Congress of the International Association for Breast Cancer Research
    • Place of Presentation
      Kurashiki, Japan
    • Related Report
      2008 Annual Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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