Re-Evaluating Breast Malignant Pleural Effusion: Toward Evidence-Based, Precision-Aligned Care with Organoids

Breast cancer–associated malignant pleural effusion (MPE) is a common and debilitating manifestation of advanced disease, yet current management is largely limited to indwelling pleural catheters and chemical pleurodesis and offers only transient palliation without addressing the underlying tumor biology. We propose that integrating patient-derived organoid modeling of pleural tumor cells with characterization via technologies like next-generation sequencing could shift MPE care from symptom management toward precision intervention. Organoid-based drug testing enables ex vivo evaluation of local therapeutic agents, including intrapleural chemotherapy, immune modulators, and bispecific antibodies, while paired genomic profiling may reveal actionable resistance pathways unique to pleural metastases. Together, these approaches could identify rational, localized combination therapies that improve local control, reduce effusion recurrence, and ultimately extend survival. By coupling functional and molecular analyses directly to the pleural compartment, we envision a translational framework that redefines breast MPE from a purely palliative condition to one amenable to mechanism-driven, patient-tailored therapy.