Annual Report 2017
Department of Breast and Medical Oncology
Toru Mukohara, Hirofumi Mukai, Yoichi Naito, Nobuaki Matsubara, Takahiro Kogawa, Kenichi Harano, Ako Hosono, Yoko Yamada, Mayuko Ito, Yumi Fujimoto, Yoriko Hasegawa
Introduction
In the Department of Breast and Medical Oncology, we are taking care of patients with breast, urologic, gynecologic, primary-unknown cancers, and sarcomas. We are also in charge of rare cancers that are difficult to be treated at other hospitals because of absence of standard therapy.
We have been contributing to development of "Ladies' Center", which will be opened in 2018 and be a core of multi-disciplinary care for women with cancer. Further, we initiated Hereditary Breast and Ovarian Cancer syndrome (HBOC) clinic to provide proper information to patients with high risk of the syndrome and to act as a bridge to Genetic Medicine and Services.
Research activities
We are implementing retrospective and prospective clinical studies as well as translational studies. We recently initiated a collaborative study with industries utilizing their technology of detecting circulating tumor cells (CTCs). Further, we played a major role in developing infrastructure as a "Cancer Genome Core Base Hospital" to implement "multiplex gene panel study for precision medicine (NCC onco-panel)".
We are also implementing clinical and translational researches with funds obtained from AMED ("Strategical research of preoperative systemic therapy for early breast cancer; PI, Mukai H) and Grant-in-Aid for Scientific Research ("3D co-culture of cancer cells in malignant effusion/CTC with adipose stem cell"; PI, Mukohara T) ("New sub-classification of triple negative breast cancer to evaluate immunogenicity"; PI, Kogawa T).
Table 1. New patients to the Department of Breast and Medical Oncology (2017)
Education
Our goal in education is to foster "genuine" medical oncologists. Graduates from our Resident/Chief Resident Programs are expected to become able to provide not only standard therapies regardless of types of cancer, but also multi-disciplinary care cooperating with other medical professionals. Obtaining skills for palliative care and dealing with oncologic emergencies are also expected. Further, we require and help them to implement clinical research to address clinical questions they find for themselves, and report the results on internal journals. That is because we want to develop scientific clinicians who can focus on issues scientifically and create evidence for themselves.
As an achievement, this year, one graduate from our residency program published an English paper as the first author, earned Diplomate, Subspecialty Board of Medical Oncology from JSMO, and obtained a faculty position in a prefectural cancer center.
Future prospects
In clinical practice, we will provide clinical care with high patient satisfaction through a multi-disciplinary team approach. In education, we will foster medical oncologists who have skills and knowledge for multi-organ oncology care and scientific acumen. In research, we will lead multi-center clinical trials and phase I to III developmental trials of investigational drugs. Further, we will expand our activity to pre-clinical research for predicting response and overcoming resistance to anti-cancer drugs. Multiple research themes are currently under discussion with industries, which we want to pursue as official researches.
List of papers published in January 2017 - March 2018
Journal
1. Yamashita Y, Tanaka Y, Kono S, Nishimura M, Mukohara T, Morinaga Y, Hara S, Takao S. Effectiveness of Pertuzumab, Trastuzumab, and Docetaxel Combination Neoadjuvant Chemotherapy for HER2-Positive Inflammatory Breast Cancer: A Case Report. Breast care (Basel, Switzerland), 12:45-47, 2017
2. Masuda H, Qi Y, Liu S, Hayashi N, Kogawa T, Hortobagyi GN, Tripathy D, Ueno NT. Reverse phase protein array identification of triple-negative breast cancer subtypes and comparison with mRNA molecular subtypes. Oncotarget, 8:70481-70495, 2017
3. Matsubara N, Mukai H, Hosono A, Onomura M, Sasaki M, Yajima Y, Hashizume K, Yasuda M, Uemura M, Zurth C. Erratum to: Phase 1 study of darolutamide (ODM-201), a new-generation androgen receptor antagonist, in Japanese patients with metastatic castration-resistant prostate cancer. Cancer Chemother Pharmacol, 80:1073-1077, 2017
4. Ueda Y, Matsubara N, Tabata KI, Satoh T, Kamiya N, Suzuki H, Kawahara T, Uemura H. Prostate-Specific Antigen Flare Phenomenon Induced by Abiraterone Acetate in Chemotherapy-Naive Patients With Metastatic Castration-Resistant Prostate Cancer. Clin Genitourin Cancer, 15:320-325, 2017
5. Watanabe J, Ito Y, Ohsumi S, Mizutani M, Tashiro H, Sakurai K, Takahashi M, Saito T, Tsurutani J, Mukai H, Yoshinami T, Takao S, Yamamoto Y, Matsuoka T, Iwase H, Iwata H, Nakamura S, Saeki T. Safety and effectiveness of eribulin in Japanese patients with locally advanced or metastatic breast cancer: a post-marketing observational study. Invest New Drugs, 35:791-799, 2017
6. Sasaki M, Izumi H, Yokoyama T, Kojima M, Hosono A. Follicular dendritic cell sarcoma treated with a variety of chemotherapy. Hematol Oncol, 35:905-908, 2017
7. Yoh K, Goto Y, Naito Y, Kishi K, Mori K, Hotta K, Hosomi Y, Yamada K, Tanai C, Tomizawa Y, Inoue A, Hasegawa Y, Nishio M, Ohashi Y, Kunitoh H. Impact of Maintenance Therapy for Patients with Non-small Cell Lung Cancer in a Real-world Setting. Anticancer Res, 37:1507-1513, 2017
8. Martin M, Holmes FA, Ejlertsen B, Delaloge S, Moy B, Iwata H, von Minckwitz G, Chia SKL, Mansi J, Barrios CH, Gnant M, Tomasevic Z, Denduluri N, Separovic R, Gokmen E, Bashford A, Ruiz Borrego M, Kim SB, Jakobsen EH, Ciceniene A, Inoue K, Overkamp F, Heijns JB, Armstrong AC, Link JS, Joy AA, Bryce R, Wong A, Moran S, Yao B, Xu F, Auerbach A, Buyse M, Chan A. Neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): 5-year analysis of a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol, 18:1688-1700, 2017
9. Shiroiwa T, Fukuda T, Shimozuma K, Mouri M, Hagiwara Y, Kawahara T, Ohsumi S, Hozumi Y, Sagara Y, Ohashi Y, Mukai H. Cost-effectiveness analysis of the introduction of S-1 therapy for first-line metastatic breast cancer treatment in Japan: results from the randomized phase III SELECT BC trial. BMC Cancer, 17:773, 2017
10. Uemura H, Matsubara N, Kimura G, Yamaguchi A, Ledesma DA, DiBonaventura M, Mohamed AF, Basurto E, McKinnon I, Wang E, Concialdi K, Narimatsu A, Aitoku Y. Erratum to: Patient preferences for treatment of castration-resistant prostate cancer in Japan: a discrete-choice experiment. BMC Urol, 17:20, 2017
11. Fukumoto T, Sakaguchi M, Oka M, Nishimura M, Mukohara T, Nishigori C. Malignant melanoma with bone marrow involvement diagnosed from hypercalcemia: Development of a neural cell adhesion molecule stain. J Dermatol, 44:e105-e106, 2017
12. Tsuchiya N, Hosono A, Yoshikawa T, Shoda K, Nosaka K, Shimomura M, Hara J, Nitani C, Manabe A, Yoshihara H, Hosoya Y, Kaneda H, Kinoshita Y, Kohashi K, Yoshimura K, Fujinami N, Saito K, Mizuno S, Nakatsura T. Phase I study of glypican-3-derived peptide vaccine therapy for patients with refractory pediatric solid tumors. Oncoimmunology, 7:e1377872, 2017
13. Nakamura N, Arahira S, Zenda S, Yoneyama K, Mukai H, Onozawa M, Toshima M, Motegi A, Hirano Y, Hojo H, Kibe Y, Akimoto T. Post-mastectomy radiation therapy without usage of a bolus may be a reasonable option. J Radiat Res, 58:66-70, 2017
14. Matsubara N, Mukai H, Hosono A, Onomura M, Sasaki M, Yajima Y, Hashizume K, Yasuda M, Uemura M, Zurth C. Phase 1 study of darolutamide (ODM-201): a new-generation androgen receptor antagonist, in Japanese patients with metastatic castration-resistant prostate cancer. Cancer Chemother Pharmacol, 80:1063-1072, 2017
15. Matsubara N, Yamada Y, Tabata KI, Satoh T, Kamiya N, Suzuki H, Kawahara T, Uemura H, Yano A, Kawakami S, Otsuka M, Fukasawa S. Comparison of Sequential Treatment With Androgen Receptor-Targeted Agent Followed by Another Androgen Receptor-Targeted Agent Versus Androgen Receptor-Targeted Agent Followed by Docetaxel in Chemotherapy-Naive Patients With Metastatic Castration-Resistant Prostate Cancer. Clin Genitourin Cancer, 15:e1073-e1080, 2017
16. Harano K, Kogawa T, Wu J, Yuan Y, Cohen EN, Lim B, Reuben JM, Ueno NT. Thrombocytosis as a prognostic factor in inflammatory breast cancer. Breast Cancer Res Treat, 166:819-832, 2017
17. Mukai H, Kogawa T, Matsubara N, Naito Y, Sasaki M, Hosono A. A first-in-human Phase 1 study of epirubicin-conjugated polymer micelles (K-912/NC-6300) in patients with advanced or recurrent solid tumors. Invest New Drugs, 35:307-314, 2017
18. Mukai H, Hagiwara Y, Imi K, Isaka H, Watanabe K, Matsuyama Y. The Impact of Treatment Preferences in Second-Line Chemotherapy on the Prognosis of HER2-Negative Metastatic Breast Cancer. Oncology, 93:315-322, 2017
19. Ohzawa H, Miki A, Teratani T, Shiba S, Sakuma Y, Nishimura W, Noda Y, Fukushima N, Fujii H, Hozumi Y, Mukai H, Yasuda Y. Usefulness of miRNA profiles for predicting pathological responses to neoadjuvant chemotherapy in patients with human epidermal growth factor receptor 2-positive breast cancer. Oncology letters, 13:1731-1740, 2017
20. Watanabe T, Kuranami M, Inoue K, Masuda N, Aogi K, Ohno S, Iwata H, Mukai H, Uemura Y, Ohashi Y. Comparison of an AC-taxane versus AC-free regimen and paclitaxel versus docetaxel in patients with lymph node-positive breast cancer: Final results of the National Surgical Adjuvant Study of Breast Cancer 02 trial, a randomized comparative phase 3 study. Cancer, 123:759-768, 2017
21. Fujii T, Kogawa T, Wu J, Sahin AA, Liu DD, Chavez-MacGregor M, Giordano SH, Raghavendra A, Murthy RK, Tripathy D, Shen Y, Yamal JM, Ueno NT. Nomogram to predict pathologic complete response in HER2-positive breast cancer treated with neoadjuvant systemic therapy. Br J Cancer, 116:509-514, 2017
22. Torres-Adorno AM, Lee J, Kogawa T, Ordentlich P, Tripathy D, Lim B, Ueno NT. Histone Deacetylase Inhibitor Enhances the Efficacy of MEK Inhibitor through NOXA-Mediated MCL1 Degradation in Triple-Negative and Inflammatory Breast Cancer. Clinical cancer research, 23:4780-4792, 2017
23. Uemura H, Matsubara N, Kinuya S, Hosono M, Yajima Y, Doi T. Safety and efficacy of radium-223 dichloride in Japanese patients with castration-resistant prostate cancer and bone metastases. Int J Clin Oncol, 22:954-963, 2017
24. Fujii S, Yamashita S, Yamaguchi T, Takahashi M, Hozumi Y, Ushijima T, Mukai H. Pathological complete response of HER2-positive breast cancer to trastuzumab and chemotherapy can be predicted by HSD17B4 methylation. Oncotarget, 8:19039-19048, 2017
25. Petrylak DP, de Wit R, Chi KN, Drakaki A, Sternberg CN, Nishiyama H, Castellano D, Hussain S, Flechon A, Bamias A, Yu EY, van der Heijden MS, Matsubara N, Alekseev B, Necchi A, Geczi L, Ou YC, Coskun HS, Su WP, Hegemann M, Percent IJ, Lee JL, Tucci M, Semenov A, Laestadius F, Peer A, Tortora G, Safina S, Del Muro XG, Rodriguez-Vida A, Cicin I, Harputluoglu H, Widau RC, Liepa AM, Walgren RA, Hamid O, Zimmermann AH, Bell-McGuinn KM, Powles T. Ramucirumab plus docetaxel versus placebo plus docetaxel in patients with locally advanced or metastatic urothelial carcinoma after platinum-based therapy (RANGE): a randomised, double-blind, phase 3 trial. Lancet, 390:2266-2277, 2017
26. Kawai A, Araki N, Naito Y, Ozaki T, Sugiura H, Yazawa Y, Morioka H, Matsumine A, Saito K, Asami S, Isu K. Phase 2 study of eribulin in patients with previously treated advanced or metastatic soft tissue sarcoma. Jpn J Clin Oncol, 47:137-144, 2017
27. Fukuoka S, Kojima T, Koga Y, Yamauchi M, Komatsu M, Komatsuzaki R, Sasaki H, Yasunaga M, Matsumura Y, Doi T, Ohtsu A. Preclinical efficacy of Sym004, novel anti-EGFR antibody mixture, in esophageal squamous cell carcinoma cell lines. Oncotarget, 8:11020-11029, 2017
28. Wang X, Reyes ME, Zhang D, Funakoshi Y, Trape AP, Gong Y, Kogawa T, Eckhardt BL, Masuda H, Pirman DA Jr, Yang P, Reuben JM, Woodward WA, Bartholomeusz C, Hortobagyi GN, Tripathy D, Ueno NT. EGFR signaling promotes inflammation and cancer stem-like activity in inflammatory breast cancer. Oncotarget, 8:67904-67917, 2017
29. Fizazi K, Tran N, Fein L, Matsubara N, Rodriguez-Antolin A, Alekseev BY, Ozguroglu M, Ye D, Feyerabend S, Protheroe A, De Porre P, Kheoh T, Park YC, Todd MB, Chi KN. Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer. N Engl J Med, 377:352-360, 2017
30. von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer. N Engl J Med, 377:122-131, 2017
31. Doi T, Shitara K, Naito Y, Shimomura A, Fujiwara Y, Yonemori K, Shimizu C, Shimoi T, Kuboki Y, Matsubara N, Kitano A, Jikoh T, Lee C, Fujisaki Y, Ogitani Y, Yver A, Tamura K. Safety, pharmacokinetics, and antitumour activity of trastuzumab deruxtecan (DS-8201), a HER2-targeting antibody-drug conjugate, in patients with advanced breast and gastric or gastro-oesophageal tumours: a phase 1 dose-escalation study. Lancet Oncol, 18:1512-1522, 2017
32. Shimokawa M, Kogawa T, Shimada T, Saito T, Kumagai H, Ohki M, Kaku T. Overall survival and post-progression survival are potent endpoint in phase III trials of second/third-line chemotherapy for advanced or recurrent epithelial ovarian cancer. J Cancer, 9:872-879, 2018
33. Hagiwara Y, Shiroiwa T, Shimozuma K, Kawahara T, Uemura Y, Watanabe T, Taira N, Fukuda T, Ohashi Y, Mukai H. Impact of Adverse Events on Health Utility and Health-Related Quality of Life in Patients Receiving First-Line Chemotherapy for Metastatic Breast Cancer: Results from the SELECT BC Study. Pharmacoeconomics, 36:215-223, 2018
34. Kawahara T, Shimozuma K, Shiroiwa T, Hagiwara Y, Uemura Y, Watanabe T, Taira N, Fukuda T, Ohashi Y, Mukai H. Patient-Reported Outcome Results from the Open-Label Randomized Phase III SELECT BC Trial Evaluating First-Line S-1 Therapy for Metastatic Breast Cancer. Oncology, 94:107-115, 2018
35. Fujii T, Matsuda N, Kono M, Harano K, Chen H, Luthra R, Roy-Chowdhuri S, Sahin AA, Wathoo C, Joon AY, Tripathy D, Meric-Bernstam F, Ueno NT. Prior systemic treatment increased the incidence of somatic mutations in metastatic breast cancer. Eur J Cancer, 89:64-71, 2018
36. Chi KN, Protheroe A, Rodriguez-Antolin A, Facchini G, Suttman H, Matsubara N, Ye Z, Keam B, Damiao R, Li T, McQuarrie K, Jia B, De Porre P, Martin J, Todd MB, Fizazi K. Patient-reported outcomes following abiraterone acetate plus prednisone added to androgen deprivation therapy in patients with newly diagnosed metastatic castration-naive prostate cancer (LATITUDE): an international, randomised phase 3 trial. Lancet Oncol, 19:194-206, 2018
37. Yamada Y, Mukai H, Tokudome Y, Kaneko M, Kashiwabara K, Wada N. Improved overall survival over recent decades in patients with hormone-receptor-positive, HER2-negative breast cancer: a single-center retrospective analysis of prognostic factors. Jpn J Clin Oncol, 48:248-254, 2018