A Triple-negative Matrix-producing Breast Carcinoma Patient-derived Orthotopic Xenograft (PDOX) Mouse Model Is Sensitive to Bevacizumab and Vinorelbine, Regressed by Eribulin and Resistant to Olaparib

• Published in: Anticancer research 2020-05, Vol.40 (5), p.2509-2514
• Main Authors: Yamamoto, Jun, Murata, Takuya, Tashiro, Yoshihiko, Higuchi, Takashi, Sugisawa, Norihiko, Nishino, Hiroto, Inubushi, Sachiko, Sun, Y U, Lim, Hyein, Miyake, Kentaro, Hongo, Atsushi, Nomura, Tsunehisa, Saitoh, Wataru, Moriya, Takuya, Tanino, Hirokazu, Hozumi, Chihiro, Bouvet, Michael, Singh, Shree Ram, Endo, Itaru, Hoffman, Robert M
• Format: Article
• Language: English
• Subjects: Adult; Animals; Bevacizumab; Bevacizumab - pharmacology; Body weight; Breast cancer; Breast carcinoma; Cell Line, Tumor; Disease Models, Animal; Drug Resistance, Neoplasm - drug effects; Female; Furans - pharmacology; Humans; Immunotherapy; Implantation; Intravenous administration; Ketones - pharmacology; Mammary gland; Mammary glands; Mice; Monoclonal antibodies; Mutation; Patients; Peritoneum; Phthalazines - pharmacology; Piperazines - pharmacology; Poly(ADP-ribose) polymerase; Surgical implants; Targeted cancer therapy; Triple Negative Breast Neoplasms - drug therapy; Triple Negative Breast Neoplasms - metabolism; Triple Negative Breast Neoplasms - pathology; Tumors; Vinorelbine; Vinorelbine - pharmacology; Xenograft Model Antitumor Assays; Xenografts; Xenotransplantation
• ISSN: 0250-7005; 1791-7530
• DOI: 10.21873/anticanres.14221

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. The MPBC PDOX model was established in the left 2 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 mm : 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. 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). Eribulin has clinical potential as treatment for triple-negative MPBC patients that are resistant to a PARP inhibitor such as olaparib.