Jun Yamamoto1,2,3, Takuya Murata4, Yoshihiko Tashiro1,2, Takashi Higuchi1,2, Norihiko Sugisawa1,2, Hiroto Nishino1,2, Sachiko Inubushi1,2, Y U Sun1,2, Hyein Lim1,2, Kentaro Miyake1,2,3, Atsushi Hongo4, Tsunehisa Nomura5, Wataru Saitoh5, Takuya Moriya6, Hirokazu Tanino7, Chihiro Hozumi8, Michael Bouvet2, Shree Ram Singh9, Itaru Endo10, Robert M Hoffman11,2. 1. AntiCancer Inc, San Diego, CA, U.S.A. 2. Department of Surgery, University of California, San Diego, CA, U.S.A. 3. Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan. 4. Department of Obstetrics and Gynecology, Kawasaki Medical School, Okayama, Japan. 5. Department of Breast and Thyroid Surgery, Kawasaki Medical School, Kurashiki, Japan. 6. Department of Pathology, Kawasaki Medical School, Kurashiki, Okayama, Japan. 7. Breast Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Japan. 8. AntiCancer Japan Inc, Narita, Japan. 9. Basic Research Laboratory, National Cancer Institute, Frederick, MD, U.S.A. all@anticancer.com singhshr@mail.nih.gov endoit@yokohama-cu.ac.jp. 10. Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan all@anticancer.com singhshr@mail.nih.gov endoit@yokohama-cu.ac.jp. 11. AntiCancer Inc, San Diego, CA, U.S.A. all@anticancer.com singhshr@mail.nih.gov endoit@yokohama-cu.ac.jp.
Abstract
BACKGROUND/AIM: Matrix-producing breast carcinoma (MPBC) is a rare and usually aggressive triple-negative breast cancer (TNBC). In this study, we determined drug sensitivity for a triple-negative MPBC, without BRCA mutations, in a patient-derived orthotopic xenograft (PDOX) model. MATERIALS AND METHODS: The MPBC PDOX model was established in the left 2nd mammary gland of nude mouse by implantation of the patient tumor using surgical orthotopic implantation (SOI). We randomized MPBC PDOX mice into 5 groups (n=5 mice/per treatment group) when the tumor volume reached 80 mm3: G1, control-no treatment; G2, bevacizumab [intra-peritoneal (i.p.), weekly, for 2 weeks]; G3, vinorelbine (i.p., weekly, for 2 weeks); G4, olaparib (oral., daily, for 2 weeks); G5, eribulin [intravenous (i.v.), weekly, for 2 weeks]. The mice in each treatment group were sacrificed on day 15. Tumor volume and body weight were measured once/week. RESULTS: The MPBC PDOX model was resistant to olaparib (p=0.22). The MPBC PDOX model treated with bevacizumab and vinorelbine showed significantly suppressed tumor growth compared to the untreated group (p=0.005 and 0.002, respectively). However, only eribulin regressed the tumor (p=0.0001). Eribulin was more effective than olaparib (p=0.0001), bevacizumab (p=0.0025) and vinorelbine (p=0.0061). CONCLUSION: Eribulin has clinical potential as treatment for triple-negative MPBC patients that are resistant to a PARP inhibitor such as olaparib. Copyright
BACKGROUND/AIM: Matrix-producing breast carcinoma (MPBC) is a rare and usually aggressive triple-negative breast cancer (TNBC). In this study, we determined drug sensitivity for a triple-negative MPBC, without BRCA mutations, in a patient-derived orthotopic xenograft (PDOX) model. MATERIALS AND METHODS: The MPBC PDOX model was established in the left 2nd mammary gland of nude mouse by implantation of the patienttumor using surgical orthotopic implantation (SOI). We randomized MPBC PDOX mice into 5 groups (n=5 mice/per treatment group) when the tumor volume reached 80 mm3: G1, control-no treatment; G2, bevacizumab [intra-peritoneal (i.p.), weekly, for 2 weeks]; G3, vinorelbine (i.p., weekly, for 2 weeks); G4, olaparib (oral., daily, for 2 weeks); G5, eribulin [intravenous (i.v.), weekly, for 2 weeks]. The mice in each treatment group were sacrificed on day 15. Tumor volume and body weight were measured once/week. RESULTS: The MPBC PDOX model was resistant to olaparib (p=0.22). The MPBC PDOX model treated with bevacizumab and vinorelbine showed significantly suppressed tumor growth compared to the untreated group (p=0.005 and 0.002, respectively). However, only eribulin regressed the tumor (p=0.0001). Eribulin was more effective than olaparib (p=0.0001), bevacizumab (p=0.0025) and vinorelbine (p=0.0061). CONCLUSION: Eribulin has clinical potential as treatment for triple-negative MPBC patients that are resistant to a PARP inhibitor such as olaparib. Copyright
Authors: Hiroto Nishino; Hannah M Hollandsworth; Norihiko Sugisawa; Jun Yamamoto; Yoshihiko Tashiro; Sachiko Inubushi; Kazuyuki Hamada; Y U Sun; Hyein Lim; Siamak Amirfakhri; Filemoni Filemoni; Robert M Hoffman; Michael Bouvet Journal: In Vivo Date: 2020 Nov-Dec Impact factor: 2.155
Authors: Kazuyuki Hamada; Yusuke Aoki; Jun Yamamoto; Chihiro Hozumi; Ming Zhao; Takuya Murata; Norihiko Sugisawa; Michael Bouvet; Takuya Tsunoda; Robert M Hoffman Journal: In Vivo Date: 2021 Nov-Dec Impact factor: 2.155