INVESTIGATIONAL THERAPIES AND TARGETED APPROACHES IN METAPLASTIC BREAST CANCER: A SYSTEMATIC REVIEW OF EMERGING PHARMACOLOGICAL STRATEGIES

Shubham N. Kanawade*, Shruti S. Aher, Rutuja R. Anarthe, Viraj D. Arote, Vaishnavi R. Arsul, Harish R. Pawar, Vishwas B. Patare

Metaplastic breast cancer (MpBC) is a rare and aggressive subtype of breast cancer characterized by significant histological heterogeneity and a poor response to conventional chemotherapy. The absence of hormone receptors and HER2 expression limits the applicability of targeted therapies used in other breast cancer subtypes, necessitating the development of novel therapeutic strategies. This systematic review aims to explore and critically evaluate recent investigational therapies and targeted pharmacological approaches currently under clinical or preclinical development for MpBC. A comprehensive literature search was conducted using PubMed, ClinicalTrials.gov, Scopus, and Web of Science databases for studies published between 2015 and 2025. The review included investigational drug trials, targeted therapies, immunotherapies, and nanotechnology-based drug delivery systems specifically evaluated for MpBC. Findings indicate that MpBC exhibits limited responsiveness to standard chemotherapy, yet several promising molecular targets have emerged, including the PI3K/mTOR axis, EGFR, PD-L1, and immune checkpoint pathways. Investigational agents such as tyrosine kinase inhibitors, PARP inhibitors, antibody–drug conjugates, and immune checkpoint inhibitors have shown early efficacy in small cohorts and early-phase clinical trials. Furthermore, advanced drug delivery platforms—such as liposomes, polymeric nanoparticles, and micelles—demonstrate potential for enhancing therapeutic targeting while minimizing systemic toxicity. However, progress is constrained by the rarity of MpBC, limited patient enrollment in trials, and heterogeneous study designs. In conclusion, investigational and precision-targeted therapies represent a promising frontier for MpBC management. Expanded clinical trial efforts and biomarker-driven approaches are essential to translate these advances into improved clinical outcomes.