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Optimization of breast cancer treatment by using stromal reaction

Research Project

Project/Area Number 15K10067
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General surgery
Research InstitutionJapanese Foundation for Cancer Research (2017-2018)
Kyorin University (2015-2016)

Principal Investigator

UENO TAKAYUKI  公益財団法人がん研究会, 有明病院 乳腺外科, 部長 (40452362)

Research Collaborator SAKURAI chie  
Project Period (FY) 2015-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsオートファジー / アポトーシス / 内分泌療法 / 化学内分泌療法 / 間質応答 / エネルギー代謝 / 血管新生 / 抗癌治療
Outline of Final Research Achievements

We found that endocrine therapy by an aromatase inhibitor (reduction in estrogen) induced autophagy but reduced apoptosis, a form of cell death. On the other hand, a chemoendocrine therapy containing endocrine therapy and oral chemotherapy (cyclophosphamide) induced not only autophagy but also apoptosis. Furthermore, tumors with stromal autophagy showed poorer response to endocrine therapy than tumors without stromal autophagy, which was not observed in chemoendocrine therapy.

Academic Significance and Societal Importance of the Research Achievements

間質のオートファジーは内分泌療法の治療反応性に影響するが、化学内分泌療法の治療反応性には影響しないことより、間質の状態を評価することにより、より効果的な治療選択が可能となると考えられる。また、治療における間質の変化をモニタリングすることにより、化学療法や分子標的治療を追加するなどの新たな治療戦略に結びつくと考えられる。とくに、術前内分泌療法後の間質の状態を評価することにより、その後の予後や追加治療の必要性が判断できる可能性があり、乳がんの予後改善につながると考えられる。

Report

(5 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (20 results)

All 2019 2018 2017 2016 2015

All Journal Article (10 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 10 results,  Open Access: 9 results,  Acknowledgement Compliant: 2 results) Presentation (10 results) (of which Int'l Joint Research: 6 results,  Invited: 5 results)

  • [Journal Article] Changes in Recurrence Score by neoadjuvant endocrine therapy of breast cancer and their prognostic implication2019

    • Author(s)
      Ueno Takayuki、Saji Shigehira、Masuda Norikazu、Iwata Hiroji、Kuroi Katsumasa、Sato Nobuaki、Takei Hiroyuki、Yamamoto Yutaka、Ohno Shinji、Yamashita Hiroko、Hisamatsu Kazufumi、Aogi Kenjiro、Sasano Hironobu、Toi Masakazu
    • Journal Title

      ESMO Open

      Volume: 4 Issue: 1 Pages: e000476-e000476

    • DOI

      10.1136/esmoopen-2018-000476

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Differential Involvement of Autophagy and Apoptosis in Response to Chemoendocrine and Endocrine Therapy in Breast Cancer: JBCRG-07TR.2019

    • Author(s)
      Ueno T, Masuda N, Kamigaki S, Morimoto T, Saji S, Imoto S, Sasano H, Toi M.
    • Journal Title

      Int J Mol Sci.

      Volume: 20 Issue: 4 Pages: 984-984

    • DOI

      10.3390/ijms20040984

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Progesterone receptor expression in proliferating cancer cells of hormone receptor-positive breast cancer.2018

    • Author(s)
      Ueno T, Saji S, Chiba T, Kamma H, Isaka H, Itoh H, Imi K, Miyamoto K, Tada M, Sasano H, Toi M, Imoto S.
    • Journal Title

      Tumour Biol.

      Volume: 40 Issue: 10 Pages: 1-10

    • DOI

      10.1177/1010428318811025

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A multicenter phase II trial of neoadjuvant letrozole plus low-dose cyclophosphamide in postmenopausal patients with estrogen receptor-positive breast cancer (JBCRG-07): therapeutic efficacy and clinical implications of circulating endothelial cells.2018

    • Author(s)
      Ueno T, Masuda N, Kamigaki S, Morimoto T, Akiyama F, Kurosumi M, Tsuda H, Mikami Y, Tanaka S, Morita S, Toi M.
    • Journal Title

      Cancer Med.

      Volume: - Issue: 6 Pages: 1516-1516

    • DOI

      10.1002/cam4.1516

    • NAID

      120006496947

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Impact of clinical response to neoadjuvant endocrine therapy on patient outcome: a follow-up study of JFMC34-0601 multicentre prospective neoadjuvant endocrine trial.2018

    • Author(s)
      Ueno T, Saji S, Masuda N, Kuroi K, Sato N, Takei H, Yamamoto Y, Ohno S, Yamashita H, Hisamatsu K, Aogi K, Iwata H, Yamanaka T, Sasano H, Toi M.
    • Journal Title

      ESMO Open.

      Volume: - Issue: 2 Pages: e000314-e000314

    • DOI

      10.1136/esmoopen-2017-000314

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A phase I/II pharmacokinetics/pharmacodynamics study of irinotecan combined with S-1 for recurrent/metastatic breast cancer in patients with selected UGT1A1 genotypes (the JBCRG-M01 study).2017

    • Author(s)
      Ishiguro H, Saji S, Nomura S, Tanaka S, Ueno T, Onoue M, Iwata H, Yamanaka T, Sasaki Y, Toi M.
    • Journal Title

      Cancer Med.

      Volume: - Issue: 12 Pages: 1258-1258

    • DOI

      10.1002/cam4.1258

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pathway level alterations rather than mutations in single genes predict response to HER2 targeted therapies in the neo-ALTTO trial.2017

    • Author(s)
      Shi W, Jiang T, Nuciforo P, Hatzis C, Holmes E, Harbeck N, Sotiriou C, Pena L, Loi S, Rosa DD, Chia S, Wardley A, Ueno T, Rossari J, Eidtmann H, Armour A, Piccart-Gebhart M, Rimm DL, Baselga J, Pusztai L.
    • Journal Title

      Ann Oncol.

      Volume: 28 Issue: 1 Pages: 128-135

    • DOI

      10.1093/annonc/mdw434

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] The lack of increases in circulating endothelial progenitor cell as a negative predictor for pathological response to neoadjuvant chemotherapy in breast cancer patients.2017

    • Author(s)
      Sunao Tanaka, Takayuki Ueno, Hiroshi Ishiguro, Satoshi Morita & Masakazu Toi
    • Journal Title

      npj Precision Oncology

      Volume: 1 Issue: 1 Pages: 6-6

    • DOI

      10.1038/s41698-017-0006-1

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinical significance of the expression of autophagy-associated marker, beclin 1, in breast cancer patients who received neoadjuvant endocrine therapy.2016

    • Author(s)
      Ueno T, Saji S, Sugimoto M, Masuda N, Kuroi K, Sato N, Takei H, Yamamoto Y, Ohno S, Yamashita H, Hisamatsu K, Aogi K, Iwata H, Imoto S, Sasano H, Toi M
    • Journal Title

      BMC Cancer

      Volume: 16 Issue: 1 Pages: 230-230

    • DOI

      10.1186/s12885-016-2270-9

    • NAID

      120005973398

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Characteristic gene expression profiles of human fibroblasts and breast cancer cells in a newly developed bilateral coculture system.2015

    • Author(s)
      Ueno T, Utsumi J, Toi M, Shimizu K
    • Journal Title

      Biomed Res Int.

      Volume: 2015 Pages: 960840-960840

    • DOI

      10.1155/2015/960840

    • NAID

      120005745649

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Neoadjuvant hormone therapy による治療最適化2018

    • Author(s)
      上野貴之
    • Organizer
      第26回日本乳癌学会学術総会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Updates on the clinical utility of 21-gene assay recurrence score (Oncotype DX).2017

    • Author(s)
      Takayuki Ueno
    • Organizer
      Organisation for Oncology and Translational Research 13th Annual Conference
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Tailored neoadjuvant endocrine therapy and chemo-endocrine therapy for postmenopausal patients with estrogen receptor-positive human epidermal growth factor receptor 2-negative primary breast cancer.2017

    • Author(s)
      Norikazu Masuda, Nobuaki Sato, Takashi Morimoto, Takayuki Ueno, et al.
    • Organizer
      2017 San Antonio Breast Cancer Symposiusm
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Circulating tumor cells: their clinical application and therapeutic potential2016

    • Author(s)
      Takayuki Ueno
    • Organizer
      The 14th Asian Breast Disease Association Meeting & Symposium
    • Place of Presentation
      福岡
    • Year and Date
      2016-09-02
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 単一細胞レベルでのバイオマーカー探索2016

    • Author(s)
      上野貴之
    • Organizer
      第24回 日本乳癌学会学術総会
    • Place of Presentation
      東京
    • Year and Date
      2016-06-16
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] Analysis of in situ expression of hormone receptors and proliferation marker at a single cell level in breast cancer tissues2016

    • Author(s)
      Takayuki Ueno, Hirotsugu Isaka, Hiroki Itoh, Kaisuke Miyamoto, Manami Kitamura, Shigeru Imoto
    • Organizer
      AACR Annual Meeting 2016
    • Place of Presentation
      New Orleans, USA
    • Year and Date
      2016-04-16
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Analysis of in situ expression of hormone receptors and proliferation marker at a single cell level in breast cancer tissues2016

    • Author(s)
      Takayuki Ueno, Hirotsugu Isaka, Hiroki Itoh, Kentaro Imi, Kaisuke Miyamoto, Manami Kitamura, Shigeru Imoto
    • Organizer
      The 4th International Conference of Federation of Asian Clinical Oncology
    • Place of Presentation
      Xiamen, China
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Analysis of in situ expression of hormone receptors and proliferation marker at a single cell level in breast cancer tissues2015

    • Author(s)
      Takayuki Ueno, Hirotsugu Isaka, Hiroki Itoh, Kentaro Imi, Kaisuke Miyamoto, Manami Kitamura, Shigeru Imoto
    • Organizer
      3rd International Conference of Federation of Asian Clinical Oncology
    • Place of Presentation
      京都
    • Year and Date
      2015-10-29
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] ER陽性乳癌組織におけるER発現とKi67発現の腫瘍内heterogeneityの解析2015

    • Author(s)
      上野貴之、伊東大樹、伊美建太郎、宮本快介、北村真奈美、井本滋
    • Organizer
      第23回日本乳癌学会学術総会
    • Place of Presentation
      東京
    • Year and Date
      2015-07-02
    • Related Report
      2015 Research-status Report
  • [Presentation] pCR再考2015

    • Author(s)
      上野貴之
    • Organizer
      第23回日本乳癌学会学術総会
    • Place of Presentation
      東京
    • Year and Date
      2015-07-02
    • Related Report
      2015 Research-status Report
    • Invited

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Published: 2015-04-16   Modified: 2020-03-30  

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