Conditional reprogrammed cells enable us to examine the drug resistance for recurrent metastatic hormone receptor-positive, human epidermal receptor 2-negative breast cancer

Objectives: Various new drugs have been developed for treating recurrent hormone receptor-positive/human epidermal receptor 2-negative breast cancer. However, directly identifying effective drugs remains difficult. In this study, we elucidated the clinical relevance of cultured cells derived from patients with recurrent hormone receptor-positive/human epidermal receptor 2-negative metastatic breast cancer. Methods: We generated conditional reprogrammed cells from primary and metastatic breast cancer. CR cells were co-cultured with irradiated mouse fibroblast feeder cells in the presence of the Rho kinase inhibitor Y-27632. We performed microarray analysis using a SurePrint G3 Human GE microarray kit Ver. 2.0, and DNA target sequence using QIAseq Targeted DNA Panels to analyze the genetic variants of the 93 most commonly mutated genes in human breast cancer samples. We examined the pathological features by xenograft model. For drug screening assay, we used Cambridge Cancer Compound Library. Results: The results of microarray analysis, DNA target sequencing and xenograft experiments indicated that the mutation status and pathological features were preserved in CR cells, whereas RNA expression was different from that in the primary tumor cells, especially with respect to cell adhesion-associated pathways. The results of drug sensitivity assays involving the use of primary breast cancer CR cells were consistent with the result of Oncotype Dx. We performed drug screening assays using liver metastases, which were sensitive to 66 drugs. The result reflected the actual clinical course of this patient, resistant to taxanes and sensitive to fulvestrant plus palbociclib. Conclusion: These results supported the use of CR cells obtained from the metastatic lesions of patients with HR+/HER2− breast cancer for predicting the clinical drug efficacy. Citation Format: Rei Mimoto, Satomi Yogosawa, Atsushi Fushimi, Hiroko Nogi, Tadashi Asakura, Kiyotsugu Yoshida, Hiroshi Takeyama. Conditional reprogrammed cells enable us to examine the drug resistance for recurrent metastatic hormone receptor-positive, human epidermal receptor 2-negative breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-03-14.