Abstract 1398: Establishment and characterization of a clinically-relevant personalized hormone-dependent breast cancer tumor model.
Authors: Wick Michael J. , Vaught Teresa L. , Gamez Lizette , Brown Jennifer , Moriarty Alyssa , Tolcher Anthony W. , Rasco Drew W. , Patnaik Amita , Rodriguez Gladys , Drengler Ronald L. , Papadopoulos Kyriakos P. 
Published: August 2014

Background: The START Patient Tumor Program was established to improve clinical outcomes for cancer patients by creating a biorepository of blood and cancer tissues for characterization and preclinical model development and testing. To date samples from over 1500 patients have been collected with over 400 models generated including 40 patient-derived breast tumor xenografts. These models can be used for personalized studies, particularly in situations where treatment options have been exhausted. In the current study a breast biopsy was collected from a 48 year old Hispanic female with recurrent, chemotherapy-refractory ER+/HER2+ metastatic breast cancer and implanted into an immune-deficient mouse. The resulting model was expanded and evaluated against eight FDA-approved and four investigational agents.

Methods: ST340 ER+/HER2+ breast PDX model: The tumor sample from an inform-consented participant was implanted into nude mice and the established model confirmed by histologic analysis and linked with clinical treatment and outcome data. Activating mutation profiling was performed on fifty-two known cancer genes with extracted DNA using a PCR-based assay with customized primers. An efficacy study was performed testing various approved and investigational agents. Study endpoints included tumor volume and time from treatment initiation. Reported results included tumor growth inhibition or delay and regression.

Results: Prior to treatment initiation, estradiol was withheld to confirm dependence and was found requisite for growth. Following treatment, results identified impressive sensitivity to the targeted therapy everolimus including tumor regressions and moderate sensitivity towards an aromatase inhibitor. Treatment with this combination regimen resulted in improved tumor markers and overall quality of life for an extended period of time. Following progression, subsequent treatment with a cytotoxic agent found active in the initial screen resulted in additional months of progression free disease. Conclusion: Participation in the START Patient Tumor Program provided beneficial data which improved clinical outcome for this patient demonstrating that personalized preclinical models of human cancer can predict useful agents for clinical treatment in select situations.

Citation Format: Michael J. Wick, Teresa L. Vaught, Lizette Gamez, Jennifer Brown, Alyssa Moriarty, Anthony W. Tolcher, Drew W. Rasco, Amita Patnaik, Gladys Rodriguez, Ronald L. Drengler, Kyriakos P. Papadopoulos. Establishment and characterization of a clinically-relevant personalized hormone-dependent breast cancer tumor model. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1398. doi:10.1158/1538-7445.AM2013-1398