Abstract 178: Establishment of patient-derived organoid of breast cancer

Abstract

Abstract A patient-derived organoid (PDO) is an in vitro three-dimensional model which shows similar features in phenotypic and genetic aspects with primary tissue from patients. PDOs are useful for preclinical studies including drug sensitivity tests of tumors from individual patients as well as development of novel targeted agents. Collectively, PDOs are recently introduced as an emerging platform for personalized medicine. We obtained a total of 100 surgical specimens from 100 patients with breast cancer at the Yonsei Cancer Center, Severance Hospital, Seoul, Korea. One of the tissue specimens was acquired from a breast cancer patient-derived xenograft model. We dissociated the tissues and isolated breast cancer primary tumor cells from the samples, and then the cells were cultured in basement membrane-like matrix in 3D manner with growth medium with supplements. We defined successful establishment of PDOs as continuous growth after 3 passaging. Among all 100 cases, 32 cases failed to culture or passage, however, 41 cases were successfully cultured over 3 passages. In addition, the remaining 27 cases are still in progress of establishment. Success rate of PDO was 68% (68/100). Subtypes of primary tumors of the PDO were 33.8% (23/68) of luminal A, 26.5% (18/68) of luminal B, 26.5% (18/68) of triple-negative, 5.9% (4/68) of triple-positive and 7.4% (5/68) of HER2-enriched. Success rates of each subtype were 69.7% (23/33) of luminal A, 72.0% (18/25) of luminal B, 66.7% (18/27) of triple-negative, 66.7% (4/6) of triple-positive and 55.6% (5/9) of HER2-enriched. Pathologic evaluation using immunohistochemistry revealed that PDOs showed similar morphologic and immunohistochemical features with primary tumors. The selective sensitivity of PARP inhibitor, olaparib, was confirmed in PDOs harboring mutant BRCA1/2 compared with BRCA1/2 wild-type PDOs. Overall, PDOs can be used as a real-time platform for drug sensitivity and screening analyses, and a robust tool for preclinical studies in breast cancer. Citation Format: Won-Ji Ryu, Shinyoung Park, Jeong Dong Lee, Yumi Hwang, Seongyeon Jo, Kweon Tae Yong, Ja Seung Koo, Min Hwan Kim, Joo Hyuk Sohn, Hyung Seok Park. Establishment of patient-derived organoid of breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 178.