Analysis of the clonal changes during neo-adjuvant chemotherapy for breast cancer and the effect on outcome of therapy.

• Project/Area Number: 15K19865
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General surgery
• Research Institution: Nagasaki University
• Principal Investigator: OIKAWA Masahiro 長崎大学, 医歯薬学総合研究科(医学系), 客員研究員 (90612416)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2017: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 腫瘍内不均一性 / 乳癌 / 術前化学療法 / circulating tumor DNA / ゲノム不安定性 / クローン交替

Outline of Final Research Achievements

Copy number analyses of five patients with SCC were conducted using array CGH technique. The cytogenetic profile of the SCC components indicated large intertumoral heterogeneity. There were between 2 and 160 copy number alterations per case, and no common copy number alterations were identified. The cytogenetic profiles of the paired SCC and NST components were similar but not identical. Although, in one case, a larger number of copy number aberrant regions were detected in the SCC component than the NST component. In this case, all of the NST component aberrations were present in the SCC component. This implies that the SCC component originated from the NST component. There were no common SCC-component-specific aberrations in the three NST-component cases. Our results demonstrate the cytogenetic inter- and intratumoral heterogeneity of SCC of the breast. Our comparison of cytogenetic profiles indicated that the SCC component originated from the NST component in one case.

Research Products

• [Journal Article] Cytogenetic analysis of metaplastic squamous cell carcinoma of the breast inter- and intratumoral heterogeneity. (2017)
  • Author(s): Oikawa M, Igawa A, Taguchi K, Baba K, Ishida M, Akiyoshi S, Yano H, Nagayasu T, Ohno S, Tokunaga E.
  • Journal Title: Breast Cancer Volume: 印刷中 Issue: 6 Pages: 733-741
  • DOI: 10.1007/s12282-017-0768-x
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Validation of a Novel Diagnostic Kit Using the Semidry Dot-Blot Method to Detect Metastatic Lymph Nodes in Breast Cancer: Distinguishing Macrometastases From Nonmacrometastases. (2017)
  • Author(s): Ryota Otsubo
  • Journal Title: Clinical breast cancer Volume: 17 Issue: 3 Pages: e345-e351
  • DOI: 10.1016/j.clbc.2017.07.009
  • Peer Reviewed / Open Access
• [Journal Article] Aromatase inhibitors with or without luteinizing hormone-releasing hormone agonist for metastatic male breast cancer: report of four cases and review of the literature. (2016)
  • Author(s): Kuba S, Ishida M, Oikawa M, Nakamura Y, Yamanouchi K, Tokunaga E, Taguchi K, Esaki T, Eguchi S, Ohno S.
  • Journal Title: Breast Cancer Volume: 23 Pages: 945-949
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Association between p53-binding protein 1 expression and genomic instability in oncocytic follicular adenoma of the thyroid (2016)
  • Author(s): Mussazhanova Z, Akazawa Y, Matsuda K, Shichijo K, Miura S, Otsubo R, Oikawa M, Yoshiura K, Mitsutake N, Rogounovitch T, Saenko V, Kozykenova Z, Zhetpisbaev B, Shabdarbaeva D, Sayakenov N, Amntayev B, Kondo H, Ito M, Nakashima M.
  • Journal Title: Endocrine Journal Volume: 63 Issue: 5 Pages: 457-467
  • DOI: 10.1507/endocrj.EJ15-0629
  • NAID: 130005154197
  • ISSN: 0918-8959, 1348-4540
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Intraoperative diagnosis of lymph node metastasis in non-small-cell lung cancer by a semi-dry dot-blot method. (2016)
  • Author(s): Tomoshige K, Tsuchiya T, Otsubo R, Oikawa M, Yamasaki N, Matsumoto K, Miyazaki T, Hayashi T, Kinoshita N, Nanashima A, Nagayasu T.
  • Journal Title: Eur J Cardiothorac Surg. Volume: 49 Issue: 2 Pages: 617-22
  • DOI: 10.1093/ejcts/ezv118
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Evaluation of totally implantable central venous access devices with the cephalic vein cut-down approach: Usefulness of preoperative ultrasonography. (2016)
  • Author(s): Otsubo R, Hatachi T, Shibata K, Yoshida T, Watanabe H, Oikawa M, Matsumoto M, Yano H, Taniguchi H, Nagayasu T.
  • Journal Title: J Surg Oncol. Volume: 113 Issue: 1 Pages: 114-9
  • DOI: 10.1002/jso.24100
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Noninvasive genomic profiling of cerebral spinal fluid in breast cancer patient with leptomeningeal disease. (2018)
  • Author(s): Masahiro Oikawa, Naveen Ramesh, Emi Sei, Shanshan Bai, Min Hu, John de Groot, Rashmi K Murthy, Barbara O’Brien, Nicholas E Navin
  • Organizer: American Association of Cancer Research (AACR) Annual Meeting 2018
  • Int'l Joint Research
• [Presentation] Cytogenetic analysis of squamous cell carcinoma of the breast reveals inter- and intra-tumoral heterogeneity. (2015)
  • Author(s): Masahiro Oikawa, Akiko Igawa, Mayumi Ishida, Yoshiaki Nakamura, Sumiko Nishimura, Chinami Koga, Sayuri Akiyoshi, Yumiko Koi, Kenichi Taguchi, Shinji Ohono, Eriko Tokunaga.
  • Organizer: San Antonio Breast Cancer Symposium 2015
  • Place of Presentation: サンアントニオ（米国）
  • Year and Date: 2015-12-08
  • Int'l Joint Research
• [Presentation] 乳腺扁平上皮癌の細胞遺伝学的プロファイルと腫瘍内不均一性の検討 (2015)
  • Author(s): 及川将弘、井川明子、石田真弓、中村吉昭、西村純子、古閑知奈美、秋吉清百合、厚井裕三子、田口健一、大野真司
  • Organizer: 第23回日本乳癌学会学術総会
  • Place of Presentation: 東京国際フォーラム（東京都）
  • Year and Date: 2015-07-02