Mechanism analysis of estrogen addition therapy for metastatic breast cancer

• Project/Area Number: 15K10057
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General surgery
• Research Institution: Kumamoto University
• Principal Investigator: Murakami Keiichi 熊本大学, 医学部附属病院, 非常勤診療医師 (20530124)
• Co-Investigator(Kenkyū-buntansha): 岩瀬 弘敬 熊本大学, 大学院生命科学研究部(医), 教授 (40211065)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 転移乳癌 / エストロゲン療法 / エストロゲン受容体 / ｃｆDNA / cfDNA / 逐次内分泌療法

Outline of Final Research Achievements

Estrogen addition therapy may be effective for metastatic breast cancer that has become resistant to ordinary endocrine therapy. We collected metastatic lesions and blood specimens of patients treated with estrogen addition therapy over time, and examined the effect prediction and mechanism of the therapy.
The estrogen receptor (ER) after estrogen depletion therapy is highly expressed in metastatic lesion in many cases and it is difficult to show the effect afterwards in cases where ER gene mutation was found in cell free DNA in the blood It has been found.

Research Products

• [Journal Article] Clinical significance of plasma cell-free DNA mutations in PIK3CA, AKT1, and ESR1 gene according to treatment lines in ER-positive breast cancer (2018)
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] Prevalence of ESR1 E380Q mutation in tumor tissue and plasma from Japanese breast cancer patients (2017)
  • 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
  • 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 patients (2017)
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] Comparison of ESR1 Mutations in Tumor Tissue and Matched Plasma Samples from Metastatic Breast Cancer Patients (2017)
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] Clinical significance of monitoring ESR1 mutations in circulating cell-free DNA in estrogen receptor positive breast cancer patients. (2016)
  • Author(s): 63.Takeshita T, Yamamoto Y, Yamamoto-Ibusuki M, Inao T, Sueta A, Fujiwara S, Omoto Y, Iwase H.
  • Journal Title: Oncotarget. Volume: 7 Issue: 22 Pages: 32504-18
  • DOI: 10.18632/oncotarget.8839
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Droplet digital polymerase chain reaction assay for screening of ESR1 mutations in 325 breast cancer specimens. (2015)
  • Author(s): Takeshita T, Yamamoto Y, Yamamoto-Ibusuki M, Inao T, Sueta A, Fujiwara S, Omoto Y, Iwase H.
  • Journal Title: Transl Res Volume: 166 Issue: 6 Pages: 540-553
  • DOI: 10.1016/j.trsl.2015.09.003
  • Peer Reviewed / Open Access
• [Presentation] Incidence and clinical relevance of&nbsp;ESR1 mutations&nbsp;in estrogen receptor positive breast cancer patients (2017)
  • Author(s): 1.Takeshita T, Tomiguchi M, Sueta A, Murakami K, Yamamoto-Ibusuki M, Yamamoto Y, Iwase H
  • Organizer: 第15回日本臨床腫瘍学会学術集会
• [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): 1.Takeshita T, Tomiguchi M, Sueta A, Murakami K, Yamamoto-Ibusuki M, Yamamoto Y, Iwase H
  • Organizer: 第76回日本癌学会学術総会
• [Presentation] 閉経後進行乳癌におけるエストロゲン枯渇療法と付加療法との交代投与法の経験 (2017)
  • Author(s): 岩瀬弘敬, 指宿睦子, 末田愛子, 竹下卓志, 富口麻衣, 山本 豊, 村上敬一
  • Organizer: 第18回ホルモンと癌研究会
• [Presentation] 乳がんホルモン療法耐性における分子標的治療の役割 (2017)
  • Author(s): 岩瀬弘敬
  • Organizer: 第21回日本がん分子標的治療学会学術集会
• [Presentation] Treatment strategy for metastatic breast cancer with estrogen receptor-positive tumor. (2017)
  • Author(s): Hirotaka Iwase
  • Organizer: 第15回日本臨床腫瘍学会学術集会 29th July, 2016 Kobe, Japan.
  • Invited
• [Presentation] Clinical significance of sequential measurements of ESR1 mutations in plasma cell-free DNA in estrogen receptor positive recurrent metastatic breast cancer patients (2016)
  • Author(s): Takeshita T, Yamamoto Y, Yamamoto-Ibusuki M, Sueta A, Tomiguchi M and Iwase H
  • Organizer: The 39th San Antonio Breast Cancer Symposium
  • Place of Presentation: S案Antonio, TX USA
  • Year and Date: 2016-12-07
  • Int'l Joint Research
• [Presentation] ESR1 gene alterations in the metastatic breast cancer with resistance to aromatase inhibitor. (2015)
  • Author(s): Iwase H, Takeshita T, Yamamoto-Ibusuki M, Inao T, Sueta A, Fujiwara S, Yamamoto Y
  • Organizer: Advances in Breast Cancer Research
  • Place of Presentation: Bellevue, Washington
  • Year and Date: 2015-10-09
  • Int'l Joint Research