Patient-Derived Organoids (PDOs) for Triple-Negative Breast Cancer: Characterization and Functional Applications

Triple negative breast cancer (TNBC), characterized by the absence of ER, PR, and HER2 expression, is among the most aggressive breast cancer subtypes. The lack of therapeutic targets severely limits treatment options, resulting in persistently poor patient prognoses. Standard treatment relies on chemotherapy, which often results in resistance and relapse, while TNBC heterogeneity and the presence of multiple molecular subtypes further complicate therapeutic strategies. Recent advances in three dimensional (3-D) culture systems, particularly patient derived organoids (PDOs), offer a physiologically relevant platform to model tumor biology, drug response, and immune interactions. As part of the Human Cancer Models Initiative (HCMI), rare PDOs that recapitulate TNBC architecture and signaling have been developed, enabling precision oncology and translational research. PDOs retained key histological and molecular features, including subtype specific HER2, PR, and ER expression, and were characterized using immunofluorescence, histology, and drug sensitivity profiling. Whole-exome sequencing confirmed genetic integrity and clinical concordance with reference datasets from The Cancer Genome Atlas, while drug screening incorporated both standard of care and targeted therapies to evaluate combination strategies. These findings underscore the ability of PDOs to more accurately model tumor heterogeneity and translational clinical concordance compared with conventional two dimensional systems. The inclusion of three expanded breast cancer models (ATCC® PDM-92™, ATCC® PDM-523™, and ATCC® PDM-411™) within the HCMI portfolio, spanning HER2⁺, ER⁺/PR⁺, and triple negative subtypes, provides a robust resource for comparative studies. The results demonstrate that patient derived TNBC organoid models faithfully recapitulate the genomic and molecular features of the originating tumors and enable the identification of mutation  and subtype specific drug response patterns, supporting functional precision oncology and the development of personalized therapeutic strategies for TNBC.