Abstract P6-03-06: Androgen supplementation in patient derived xenografts in androgen receptor positive breast cancer to increase engraftment and growth rate

Abstract

Abstract Background: The European fund for regional development (EFRE) supported Precision Oncology and Personalized Therapy Prediction (POP) Project is establishing preclinical models to further the development of personalized therapy options. In the subgroup breast cancer the current goal is to increase the growth and engraftment rates of breast cancer patient derived xenografts (PDX) models. Methods: Breast cancer patients of the Department of Gynecology with Breast Center Charité Universitätsmedizin Berlin, Germany are recruited since May 2017. In total 29 tissue samples were collected and included so far. Treatment naive and treatment refractory patients, tripple negative breast cancer (TNBC), hormone receptor positive (HR+) and Her2 postivie tumors, primary disease, recurrence or metastasis are sampled. Fresh tumor tissue is extracted via surgery or biopsy. The materials are then implanted into female immunodeficient NOG mice. To establish PDX models for HR+ breast cancer the mice received estrogen supplementation. To increase engraftment and growth rates androgen receptor (AR) testing and subsequently androgen replacement was started since April 2018. Up to date, 6 new samples have been collected. One HR+ and two TNBC samples tested also positive for AR. These samples are currently in passage 0 (p0) and are now supplied with androgens to increase engraftment and growth rate. One already established AR+ TNBC PDX is being regrown with androgen supplementation to compare growth rates. Results: Out of the initial 23 tissue samples ten (six HR+ and four TNBC) have been able to be engrafted into PDX mice. The TNBC PDX models are one in p1, one in p2, one in p3 and one is being tested with systemic therapy. Engraftment time in p1 were between 19 and 97 days. Growth time to passagable size between 21 and 112 days. The HR+ PDX models are four in p1 and two in p2. Engraftment time in p1 was between 26 and 123 days. Growth time to passagable size has been achieved in 2 HR+ PDX within 17 to 48 days. The engraftment/growth rates and times of the androgen supplemented PDX models will be presented. Conclusion: Breast cancer growths in humans slowly and this is also the case in the PDX models. To achieve faster growth and higher engraftment rates androgen supplementation in AR+ breast cancer might be an additional enhancive factor. Citation Format: Kiver VII, Wulf-Goldenberg A, Jurmeister PS, Schweiger C, Gorea O, Hoffmann J, Denkert C, Keilholz U, Liedtke C, Blohmer J-U. Androgen supplementation in patient derived xenografts in androgen receptor positive breast cancer to increase engraftment and growth rate [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-03-06.