The Organoid Decade: Leveraging 3D Patient-Derived Organoids to Bridge the Translational Gap in Triple-Negative Breast Cancer: A Systematic Review

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with limited effective therapies. Two-dimensional (2D) in vitro models poorly recapitulate tumor microenvironment (TME) interactions, impeding the translational relevance of TNBC immunotherapy research. Three-dimensional patient-derived tumor organoids (3D PDTOs) have emerged as advanced preclinical models that better mimic tumor–immune interactions. The objective of this systematic review was to assess the landscape of 3D PDTO adoption in TNBC research and evaluate their application in addressing key bottlenecks in TNBC immunotherapy. We retrieved 394 studies published between 2015 and 2025 from the PubMed and ClinicalTrials.gov databases. Of those, 153 studies were included in the review. Fifty-eight (58) TNBC-specific studies met the inclusion criteria, including explicit mention of 3D PDTOs in the title or abstract, with confirmation in the Methods and Results sections. Studies were excluded if they used non-patient-derived tumor organoids or referred to other 3D models as 3D PDTOs. Data were collected from January 2025 through December 2025. Eligible studies were screened in three (3) tiers, grouped by relevant themes and graphed in Excel. We present an overview of the adoption of 3D PDTOs in TNBC research, highlighting the most common application trends within this scope. We also discuss the potential impact of artificial intelligence (AI) and regulatory guidance from the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMA) pertinent to the adoption of organoids as human-relevant models to improve translational outcomes. Overall, this review provides actionable insights for leveraging 3D PDTOs to advance translational TNBC research and precision oncology.