Organoid forming potential as complementary parameter for accurate evaluation of breast cancer neoadjuvant therapeutic efficacy

• Published in: British journal of cancer Vol. 130; no. 7; pp. 1109 - 1118
• Main Authors: Ye, Hai-Shan, Zhou, Dan, Li, Hong, Lv, Jin, Huang, Hui-Qi, She, Jia-Jun, Nie, Jun-Hua, Li, Ting-Ting, Lu, Meng-Di, Du, Bo-Le, Yang, Shu-Qing, Chen, Pei-Xian, Li, Sheng, Ye, Guo-Lin, Luo, Wei, Liu, Jia
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 20.04.2024; Nature Publishing Group
• Subjects: 692/499; 692/699/67; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biomedical and Life Sciences; Biomedicine; Breast cancer; Breast Neoplasms - pathology; Cancer Research; Disease-Free Survival; Drug Resistance; Epidemiology; ErbB-2 protein; Female; Humans; Molecular Medicine; Neoadjuvant Therapy; Oncology; Organoids; Phenotypes; Receptor, ErbB-2; Tumors
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/s41416-024-02595-w

Background 13–15% of breast cancer/BC patients diagnosed as pathological complete response/pCR after neoadjuvant systemic therapy/NST suffer from recurrence. This study aims to estimate the rationality of organoid forming potential/OFP for more accurate evaluation of NST efficacy. Methods OFPs of post-NST residual disease/RD were checked and compared with clinical approaches to estimate the recurrence risk. The phenotypes of organoids were classified via HE staining and ER, PR, HER2, Ki67 and CD133 immuno-labeling. The active growing organoids were subjected to drug sensitivity tests. Results Of 62 post-NST BC specimens, 24 were classified as OFP-I with long-term active organoid growth, 19 as OFP-II with stable organoid growth within 3 weeks, and 19 as OFP-III without organoid formation. Residual tumors were overall correlated with OFP grades ( P  < 0.001), while 3 of the 18 patients (16.67%) pathologically diagnosed as tumor-free (ypT0N0M0) showed tumor derived-organoid formation. The disease-free survival/DFS of OFP-I cases was worse than other two groups (Log-rank P  < 0.05). Organoids of OFP-I/-II groups well maintained the biological features of their parental tumors and were resistant to the drugs used in NST. Conclusions The OFP would be a complementary parameter to improve the evaluation accuracy of NST efficacy of breast cancers.