Breast cancer organoids from malignant pleural effusion-derived tumor cells as an individualized medicine platform

• Published in: In vitro cellular & developmental biology. Animal Vol. 57; no. 5; pp. 510 - 518
• Main Authors: Pan, Bo, Zhao, Dongyi, Liu, Yaqian, Li, Na, Song, Chen, Li, Ning, Li, Xuelu, Zhao, Zuowei
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.05.2021; Society for In Vitro Biology
• Subjects: 5-Fluorouracil; Adult; Animal Genetics and Genomics; Antigens; Antineoplastic Agents - therapeutic use; Biomarkers; Biomedical and Life Sciences; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Cell Biology; Cell Culture; Clavicle; Culture; Developmental Biology; Drug screening; Epidermal growth factor; Estrogen receptors; Estrogens; Female; Gene polymorphism; Growth factors; Health services; Humans; Life Sciences; Lymph nodes; Lymph Nodes - pathology; Metastases; Metastasis; Methylenetetrahydrofolate reductase; Mutation; Next-generation sequencing; Organoids; Organoids - drug effects; Organoids - pathology; Patients; Pleural effusion; Pleural Effusion, Malignant - cytology; Pleural Effusion, Malignant - pathology; Polymorphism; Precision Medicine - methods; Progesterone; Receptors; Stem Cells; Treatment Outcome; Triple Negative Breast Neoplasms - drug therapy; Triple Negative Breast Neoplasms - pathology; Triple Negative Breast Neoplasms - therapy; Tumor cells; Tumors; Pleural effusion; Drug sensitivity test; Individualized therapy; Organoid culture; Triple-negative breast cancer
• ISSN: 1071-2690; 1543-706X
• DOI: 10.1007/s11626-021-00563-9

Malignant pleural effusion (MPE) presents a severe medical condition in patients with advanced breast cancer (BC). We applied organoid culture technology to culture preoperative puncture specimen and corresponding surgical specimen-derived tumor cells from early BC patients and pleural effusion-derived tumor cells from advanced BC patients with MPE to study whether in vitro models could predict therapies of clinical patients. We successfully expanded pleural effusion-derived tumor organoids from 1 advanced triple-negative breast cancer (TNBC) patient with MPE which had been continuously propagated for more than 3 months. The organoids matched the histological characteristics of primary BC and metastatic supraclavicular lymph nodes by H&E staining and retained negative expression of TNBC biomarkers: estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, and positive expression of antigen Ki-67. Multiple mutations were detected from this advanced TNBC patient with MPE by high-throughput sequencing of metastatic supraclavicular lymph node and the plasma sample. We performed the 3D drug screening tests combined with the clinical medication situation of this patient. The pleural effusion-derived tumor organoids were sensitive to capecitabine (IC 50 1.580 μmol) and everolimus (IC 50 4.008 μmol) single-agent treatments. The sensitivity to capecitabine was consistent with the clinical treatment response of this patient for capecitabine and with the sequencing results that reported MTHFR gene polymorphism mutation and TYMS −6bp/−6bp polymorphism mutation indicating effectiveness to fluorouracil. Our results suggested that an effective platform for ex vivo pleural effusion-derived tumor organoids from advanced TNBC patients with MPE could be used to identify treatment options and explore the clinicopathological characteristics of these patients.