Abstract 1049: Orthotopic implantation of aggressive breast cancer achieves better engraftment and larger tumor in patient-derived xenograft models

• Published in: Cancer research (Chicago, Ill.) Ill.), 2018-07, Vol.78 (13_Supplement), p.1049-1049
• Main Authors: Okano, Maiko, Kawaguchi, Tsutomu, Takabe, Kazuaki
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2018-1049

Background: Breast cancer patient-derived xenograft (PDX) has come into the limelight to address the issue of intratumoral heterogeneity in preclinical studies; however, there are still some unsolved problems regarding its practical usage in translational research. There are no systematic studies that clarify the advantage of orthotopic implantation of the tumor as opposed to ectopic, or of the type of source tumor. Thus, we investigated the difference of tumor growth caused by these variables among breast cancer PDX model mice. Methods: We xenografted 10 patient breast cancer tumors into NSG mice. 2 tumors were derived from brain metastasis (B-met), whereas the others were from primary. 3 tumors were ER(+) HER2(-) and 7 tumors were triple negative (TN). Both of b-met tumors are ER(+) HER2(-). Using 2-3 mice per each patient sample, about 1mm3 tumor fragments were implanted surgically into four subcutaneous (SQ) sites ectopically and four sites (bilateral 2nd and 4th mammary fat pad) orthotopically (Orth). Tumors were passaged to another 2-4 mice as the next generation when the largest tumor grew to 1.5cm in diameter. Tumor “take” was defined as tumorigenesis of palpable tumor after implantation regardless of time it took. Results: PDX tumors were established in 7 out of 10 patient tumors. Histologic grade 3 tumors have significantly higher take rate than grade 2 tumors in 1st generation (3.4% [1/29 site] vs 51.9% [56/108 site], p