Abstract
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.
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Data availability
The data generated in this study are available within the article and its supplementary data files.
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Acknowledgements
We thank Jian-Li He and Xuan Luo for their technical support and insightful discussions.
Funding
This work was supported by grants from the Special Fund of Foshan Summit Plan (NO. 2020B018, 2019D039, and 2019D041), the National Natural Science Foundation of China (No. 81272786 and 81450016), and the Special Fund of South China University of Technology from Central Government of China.
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H.L., D.Z., G.L.Y., W.L., and J.L., conceived and designed the experiments; D.Z., S.Q. Y., H.Q.H., J.J.S., and P.X.C. recruited the patients, provided the resected tissues, and collected clinical information; J.L., evaluated the pathologic outcome after neoadjuvant and organoid pathological identification; H.S.Y., J.H.N., M.D.L., T.T.L., B.L.D., and S.L. performed the experiments, analyzed the data and edited the figures; H.S.Y. wrote the manuscript; All the authors critically reviewed the manuscript. The work reported in the paper has been performed by the authors, unless clearly specified in the text.
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Specimen collection and research contents were examined and approved by the Research Ethics Committee of Foshan First People’s Hospital (L [2021] NO. 9). All procedures are carried out by the Helsinki Declaration.
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Ye, HS., Zhou, D., Li, H. et al. Organoid forming potential as complementary parameter for accurate evaluation of breast cancer neoadjuvant therapeutic efficacy. Br J Cancer 130, 1109–1118 (2024). https://doi.org/10.1038/s41416-024-02595-w
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DOI: https://doi.org/10.1038/s41416-024-02595-w