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Investigation of molecular markers for prediction of the highly aggressive breast cancers that show clinically progressive disease during neoadjuvant chemotherapy

Research Project

Project/Area Number 25430144
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Tumor diagnostics
Research InstitutionNational Defense Medical College

Principal Investigator

TSUDA HITOSHI  防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究, 病態病理学, 教授 (70217321)

Research Collaborator Yoshida Masayuki  国立がん研究センター中央病院, 病理科・臨床検査科
Kinoshita Takayuki  国立がん研究センター中央病院, 乳腺外科, 科長
Tamura Kenji  国立がん研究センター中央病院, 乳腺・腫瘍内科, 科長
Ono Makiko  国立がん研究センター中央病院, 乳腺・腫瘍内科
Tanabe Yuko  国立がん研究センター中央病院, 乳腺・腫瘍内科
Project Period (FY) 2013-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords乳癌 / 化学療法抵抗性 / 上皮間葉移行 / トリプルネガティブ乳癌 / 術前化学療法 / 臨床的病状進行 / バイオマーカー / 免疫組織化学 / ゲノム / 化生を伴う癌 / 化学療法効果予測 / 化生癌
Outline of Final Research Achievements

Using surgically resected tumor specimens from 22 TNBCs that showed cPD during NAC (cPD group) and 80 TNBCs that did not receive NAC (control group), we performed histopathologic and immunohistochemical (IHC) analyses of 11 molecules relevant to epithelial-mesenchymal transition (EMT), basal-like, molecular apocrine or other features. Metaplastic features and high proliferation on histology and positive cytokeratin 5/6, ZEB1, TWISTNB, vimentin, and HMGB1 and negative androgen receptor (AR) by IHC were more frequent in the cPD than in the control. By an unsupervised hierarchical cluster analysis incorporating these 11 molecules, the 102 TNBCs were divided into two major clusters and seven subclusters that appeared to correspond to intrinsic subtype, cPD status, histological type, and clinical outcome. The combinations of high proliferation, metaplastic features, and statuses of some EMT and basal-like markers and AR appeared to characterize the TNBCs that showed cPD after NAC.

Report

(5 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (19 results)

All 2017 2016 2015 2014

All Journal Article (11 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 11 results,  Acknowledgement Compliant: 5 results,  Open Access: 4 results) Presentation (7 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results) Book (1 results)

  • [Journal Article] Prognostic significance of progesterone receptor expression in estrogen-receptor positive, HER2-negative, node-negative invasive breast cancer with a low Ki-67 labeling index2017

    • Author(s)
      Makiko Ono, Hitoshi Tsuda, Masayuki Yoshida, Chikako Shimizu, Takayuki Kinoshita, Kenji Tamura
    • Journal Title

      Clin Breast Cancer

      Volume: 17 Issue: 1 Pages: 41-47

    • DOI

      10.1016/j.clbc.2016.06.012

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Prognostic and predictive values of PD-1 and PD-L1 expression among patients who received neoadjuvant chemotherapy in early breast cancer2017

    • Author(s)
      Atsuko Kitano, Makiko Ono, Masayuki Yoshida, Emi Noguchi, Akihiko Shimomura, Tatsunori Shimoi, Mayu Yonokawa, Kan Yonemori, Chikako Shimizu, Takayuki Kinoshita, Yasuhiro Fujiwara, Hitoshi Tsuda, Kenji Tamura
    • Journal Title

      ESMO Open

      Volume: 2 Issue: 2 Pages: e000150-e000150

    • DOI

      10.1136/esmoopen-2016-000150

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Histopathological and immunohistochemical characteristics of triple-negative breast cancers that showed clinically progressive disease during neoadjuvant chemotherapy2017

    • Author(s)
      Yuko Tanabe, Hitoshi Tsuda, Masayuki Yoshida, Harukaze Yamamoto, Makoto Kodaira, Mayu Yunokawa, Kan Yonemori, Chikako Shimizu, Seiichiro Yamamoto, Takayuki Kinoshita, Yasuhiro Fujiwara, Kenji Tamura
    • Journal Title

      Cancer Sci

      Volume: in press Issue: 7 Pages: 1520-1529

    • DOI

      10.1111/cas.13274

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Prognostic impact of discordance in hormone receptor status between primary and recurrent sites in the patients with recurrent breast cancer2016

    • Author(s)
      Sho Shiino, Takayuki Kinoshita, Masayuki Yoshida, Kenjiro Jimbo, Sota Asaga, Shin Takayama, Hitoshi Tsuda
    • Journal Title

      Clin Breast Cancer

      Volume: 16 Issue: 4 Pages: e133-e140

    • DOI

      10.1016/j.clbc.2016.05.014

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Clinicopathological predictive factors of ipsilateral and contralateral events in ductal carcinoma in situ after initial surgical therapy2016

    • Author(s)
      Nobuko Tamura, Hitoshi Tsuda, Junko Suzuki, Kenjiro Jimbo, Sota Asaga, Takashi Hojo, and Takayuki Kinoshita
    • Journal Title

      Breast Cancer

      Volume: 23 Issue: 3 Pages: 510-518

    • DOI

      10.1007/s12282-015-0595-x

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Prognostic impact of discordance in hormone receptor status between primary and recurrent sites in the patients with recurrent breast cancer2016

    • Author(s)
      Sho Shiino, Takayuki Kinoshita, Masayuki Yoshida, Kenjiro Jimbo, Sota Asaga, Shin Takayama, and Hitoshi Tsuda
    • Journal Title

      Clin Breast Cancer

      Volume: in press

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Expression of ribophorin II (RPN2) in human breast cancer2015

    • Author(s)
      Makiko Ono, Hitoshi Tsuda, Takayuki Kobayashi, Fumitaka Takeshita, Ryou-u Takahashi, Kenji Tamura, Sadako Akashi-Tanaka, Tomoyuki Moriya, Tamio Yamasaki, Takayuki Kinoshita, Junji Yamamoto, Yasuhiro Fujiwara, and Takahiro Ochiya
    • Journal Title

      Pathology International

      Volume: 65 Issue: 6 Pages: 301-308

    • DOI

      10.1111/pin.12297

    • Related Report
      2015 Research-status Report 2014 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Prognostic impact of Ki-67 labeling indices with three different cut-off values and histological and nuclear grades in hormone-receptor- positive, HER2-negative, node-negative invasive breast cancers.2015

    • Author(s)
      Makiko Ono, Hitoshi Tsuda, Mayu Yunokawa, Kan Yonemori, Chikako Shimizu, Masashi Ando, Kenji Tamura, Takayuki Kinoshita, Yasuhiro Fujiwara
    • Journal Title

      Breast Cancer

      Volume: (in press) Issue: 2 Pages: 141-152

    • DOI

      10.1007/s12282-013-0464-4

    • Related Report
      2014 Research-status Report 2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Clinicopathological predictive factors of ipsilateral and contralateral events in ductal carcinoma in situ after initial surgical therapy2015

    • Author(s)
      Nobuko Tamura, Hitoshi Tsuda, Junko Suzuki, Kenjiro Jimbo, Sota Asaga, Takashi Hojo, Takayuki Kinoshita
    • Journal Title

      Breast Cancer

      Volume: in press

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Activated PI3K/AKT and MAPK pathways are potential good prognostic markers in node-positive, triple-negative breast cancer2014

    • Author(s)
      Kenji Hashimoto, Hitoshi Tsuda, Fumiaki Koizumi, Chikako Shimizu, Kan Yonemori, Masashi Ando, Makoto Kodaira, Mayu Yunokawa, Yasuhiro Fujiwara, Kenji Tamura
    • Journal Title

      Annals of Oncology

      Volume: 25 Issue: 10 Pages: 1973-1979

    • DOI

      10.1093/annonc/mdu247

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Nucleostemin expression in invasive breast cancer2014

    • Author(s)
      Takayuki Kobayashi, Kenkichi Masutomi, Kenji Tamura, Tomoyuki Moriya, Tamio Yamasaki, Yasuhiro Fujiwara, Junji Yamamoto, Osamu Matsubara, Hitoshi Tsuda
    • Journal Title

      BMC Cancer

      Volume: 14(1) Issue: 1 Pages: 215-215

    • DOI

      10.1186/1471-2407-14-215

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] Immune system pathway activation for prediction of the response to neoadjuvant chemotherapy in triple-negative breast cancer2017

    • Author(s)
      Takeshi Sawada, Riet Hilhorst, Savithri Rangarajan, Masayuki Yoshida, Kenji Tamura, Rinie van Beuningen, Rob Ruijtenbeek, Hitoshi Tsuda, Fumiaki Koizumi
    • Organizer
      AACR Annual Meeting 2017
    • Place of Presentation
      Washington D. C., U. S. A.
    • Year and Date
      2017-04-01
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 臓器別シンポジウム:乳がん治療のゲノム個別化を促進する.乳癌の微小免疫環境と治療感受性について2015

    • Author(s)
      津田均、田辺裕子、木下貴之、田村研治
    • Organizer
      第53回日本癌治療学会
    • Place of Presentation
      京都
    • Year and Date
      2015-10-29
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] 乳がん再発に関与するLong Non-coding RNAの探索2015

    • Author(s)
      竹下文隆、小野麻紀子、高橋陵宇、津田均、田村研治、落谷孝広
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-10-08
    • Related Report
      2015 Research-status Report
  • [Presentation] 術前化学療法抵抗性トリプルネガティブ乳癌におけるHMGB1 発現の検討2015

    • Author(s)
      田辺裕子、津田 均、吉田正行、木下貴之、公平 誠、 温泉川真由、山本春風、米盛勧、清水千佳子、藤原康弘、田村研治
    • Organizer
      第23回日本乳癌学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      2015-07-02
    • Related Report
      2015 Research-status Report
  • [Presentation] Tumor-infiltrating lymphocyte and cytoplasmic HMG1 expression in triple-negative breast cancers that progress during neoadjuvant chemotherapy2015

    • Author(s)
      Yuko Tanabe, Hitoshi Tsuda, Masayuki Yoshida, Makoto Kodaira, Mayu Yunokawa, Kan Yonemori, Harukaze Yamamoto, Chikako Shimizu, Yasuhiro Fujiwara, Kenji Tamura
    • Organizer
      St Gallen Breast Cancer Symposium 2015
    • Place of Presentation
      Vienna, Austria
    • Year and Date
      2015-03-18 – 2015-03-21
    • Related Report
      2014 Research-status Report
  • [Presentation] 術前化学療法中に病状進行を認めるトリプルネガティブ乳癌の臨床病理所見の検討2014

    • Author(s)
      田辺裕子、津田均、吉田正行、木下貴之、橋本淳、公平誠、温泉川真由、米盛勧、山本春風、清水千佳子、藤原康弘、田村研治
    • Organizer
      第73回日本癌学会総会
    • Place of Presentation
      横浜
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Research-status Report
  • [Presentation] Histopathologic and immunohistochemical findings in triple-negative breast cancers showing clinical progressive disease during neoadjuvant chemotherapy2014

    • Author(s)
      Yuko Tanabe, Hitoshi Tsuda, Masayuki Yoshida, Makoto Kodaira, Mayu Yunokawa, Kan Yonemori, Harukaze Yamamoto, Chikako Shimizu, Yasuhiro Fujiwara, Kenji Tamura
    • Organizer
      The 50th Annual Meeting of American Society of Clinical Oncology (2014 ASCO Meeting)
    • Place of Presentation
      San Antonio, TX, U.S.A.
    • Year and Date
      2014-05-30 – 2014-06-03
    • Related Report
      2014 Research-status Report 2013 Research-status Report
  • [Book] 乳癌診療のための分子病理エッセンシャル2016

    • Author(s)
      津田 均、田村研治、木下貴之
    • Total Pages
      304
    • Publisher
      南山堂
    • Related Report
      2016 Annual Research Report

URL: 

Published: 2014-07-25   Modified: 2019-07-29  

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