Elucidation of Molecular Mechanisms of Biological Heterogeneity and Its Clinical Application in Triple-Negative Breast Cancer.

• Project/Area Number: 16K19899
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General surgery
• Research Institution: Kyushu University
• Principal Investigator: YAMASHITA Nami 九州大学, 大学病院, 助教 (60608967)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: トリプルネガティブ乳癌 / EMT / collective invasion / E-cadherin / vimentin / BRCAness / cancer invasion / heterogeneity / BRCA1 dysfunction / BRCA1プロモーターメチル化 / ゲノム不安定性 / 多様性 / BRCA1機能異常

Outline of Final Research Achievements

The treatment of patients with TNBC has been challenging due to the absence of
these molecular targets and the heterogeneity of the disease. Multiple mechanisms have emerged to address how epithelial breast tumors invade. The aim of our study is to elucidate the　clinical importance of the expression of E-cadherin and vimentin in breast cancer. Co-expression of E-cadherin and vimentin seems to be associated with the most aggressive phenotype and poorest prognosis in breast cancer. Moreover, co-localization of E-cadherin and vimentin within the same breast cancer cells indicates the existence of heterogeneity in breast cancer invasion.The therapeutic targeting of aggressive subpopulation may provide a positive impact on improving the outcomes of breast cancer patients.

Research Products

• [Journal Article] Epithelial Paradox: Clinical Significance of Coexpression of E-cadherin and Vimentin With?Regard to Invasion and Metastasis of Breast?Cancer (2018)
  • Author(s): Yamashita Nami、Tokunaga Eriko、Iimori Makoto、Inoue Yuka、Tanaka Kimihiro、Kitao Hiroyuki、Saeki Hiroshi、Oki Eiji、Maehara Yoshihiko
  • Journal Title: Clinical Breast Cancer Volume: 印刷中 Issue: 5 Pages: e1003-e1009
  • DOI: 10.1016/j.clbc.2018.02.002
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Protein Expression of Programmed Death 1 Ligand 1 and HER2 in Gastric Carcinoma (2017)
  • Author(s): Oki Eiji、Okano Shinji、Saeki Hiroshi、Umemoto Yuichiro、Teraishi Koji、Nakaji Yu、Ando Koji、Zaitsu Yoko、Yamashita Nami、Sugiyama Masahiko、Nakashima Yuichiro、Ohgaki Kippei、Oda Yoshinao、Maehara Yoshihiko
  • Journal Title: Oncology Volume: 93 Issue: 6 Pages: 387-394
  • DOI: 10.1159/000479231
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Clinical Significance of the Wild Type p53-Induced Phosphatase 1 Expression in Invasive Breast Cancer (2017)
  • Author(s): Inoue Yuka、Yamashita Nami、Kitao Hiroyuki、Tanaka Kimihiro、Saeki Hiroshi、Oki Eiji、Oda Yoshinao、Tokunaga Eriko、Maehara Yoshihiko
  • Journal Title: Clinical Breast Cancer Volume: 印刷中 Issue: 4 Pages: e643-e650
  • DOI: 10.1016/j.clbc.2017.11.008
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] The relationship between the expression of FOXA1 and GATA3 and the efficacy of neoadjuvant endocrine therapy. (2017)
  • Author(s): Tanaka K, Tokunaga E, Yamashita N, Sagara Y, Ohi Y, Taguchi K, Ohno S, Okano S, Oda Y, Maehara Y.
  • Journal Title: Breast Cancer Volume: 24 Issue: 3 Pages: 384-392
  • DOI: 10.1007/s12282-016-0714-3
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] The impact of the expression of vimentin and Axl in breast cancer. (2016)
  • Author(s): Tanaka K, Tokunaga E, Inoue Y, Yamashita N, Saeki H, Okano S, Kitao H, P Oki E, Oda Y, Maehara Y.
  • Journal Title: Clin Breast Cancer Volume: 16 Issue: 6 Pages: 520-526
  • DOI: 10.1016/j.clbc.2016.06.015
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Biological and clinical significance of loss of heterozygosity at the INPP4B gene locus in Japanese breast cancer. (2016)
  • Author(s): Tokunaga E, Yamashita N, Kitao H, Tanaka K, Taketani K, Inoue Y, Saeki H, Oki E, Oda Y, Maehara Y.
  • Journal Title: The Breast Volume: 26 Pages: 62-68
  • DOI: 10.1016/j.breast.2015.10.006
  • Peer Reviewed
• [Journal Article] Expression of APOBEC3B mRNA in Primary Breast Cancer of Japanese Women. (2016)
  • Author(s): Tokunaga E, Yamashita N, Tanaka K, Inoue Y, Akiyoshi S, Saeki H, Oki E, Kitao H, Maehara Y.
  • Journal Title: PLoS One Volume: 11 Issue: 12 Pages: e0168090-e0168090
  • DOI: 10.1371/journal.pone.0168090
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] The clinical impact of the Prognostic Nutritional Index (PNI) and Controlling Nutritional Status (CONUT) score on breast cancer patients survival. (2017)
  • Author(s): Nami Yamashita, Yuka Inoue, Kimihiro Tanaka, Hiroshi Saeki, Eiji Oki, Eriko Tokunaga, Yoshihiko Maehara
  • Organizer: ASCO annual meeting 2017
  • Int'l Joint Research
• [Presentation] Epithelial paradox; 乳癌細胞におけるE-cadherinとvimentinの共局在の意義 (2017)
  • Author(s): 山下奈真, 徳永えり子, 井上有香, 田中仁寛, 佐伯浩司, 沖英次, 前原喜彦
  • Organizer: 第25回日本乳癌学会学術総会
• [Presentation] The clinical impact of the PD-L1 expression and immunonutritional status on breast cancer survival (2017)
  • Author(s): Nami Yamashita, Eriko Tokunaga, Yuka Inoue, Hiroshi Saeki, Eiji Oki, Yoshihiko Maehara
  • Organizer: 第76回日本癌学会学術総会
• [Presentation] The comparison of clinical impact of the Prognostic Nutritional Index (PNI) and Controlling Nutritional Status (CONUT) score on breast cancer patients’ survival. (2017)
  • Author(s): Nami Yamashita, Yuka Inoue, Hiroshi Saeki, Eiji Oki, Eriko Tokunaga, Yoshihiko Maehara
  • Organizer: 第54回日本癌治療学会学術総会
• [Presentation] Epithelial paradox; clinical significance of co-expression of E-cadherin and vimentin in the invasion and the metastasis of breast cancer. (2016)
  • Author(s): Nami Yamashita, Eriko Tokunaga, Yuka Inoue, Kimihiro Tanaka, Hiroshi Saeki, Eiji Oki, Yoshihiko Maehara
  • Organizer: San Antonio Breast Cancer Symposium 2016
  • Place of Presentation: Texas
  • Year and Date: 2016-12-06
  • Int'l Joint Research
• [Presentation] Epithelial paradox; clinical significance E-cadherin and vimentin expression pattern in invasive breast cancer. (2016)
  • Author(s): Nami Yamashita, Eriko Tokunaga, Yuka Inoue, Kimihiro Tanaka, Hiroshi Saeki, Eiji Oki, Yoshihiko Maehara
  • Organizer: 第75回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2016-10-06
• [Presentation] Epithelial paradox; clinical significance of E-cadherin and vimentin expression pattern in invasive breast cancer. (2016)
  • Author(s): Nami Yamashita, Eriko Tokunaga, Yuka Inoue, Kimihiro Tanaka, Hiroshi Saeki, Eiji Oki, Yoshihiko Maehara
  • Organizer: The 14th Asian Breast Diseases Association
  • Place of Presentation: Fukuoka
  • Year and Date: 2016-09-02
  • Int'l Joint Research / Invited
• [Presentation] Epithelial paradox; 浸潤性乳管癌における浸潤形態のheterogeneityについて (2016)
  • Author(s): 山下奈真、徳永えり子、井上有香、田中仁寛、上尾裕紀、前原喜彦
  • Organizer: 第23回日本乳癌学会学術総会
  • Place of Presentation: 東京
  • Year and Date: 2016-06-16