Recent Advances in Malignant Phyllodes Tumors of the Breast.

Phyllodes tumors (PTs) represent an uncommon category of fibroepithelial neoplasms found in the breast tissue and are classified as benign, borderline, or malignant based on their histopathological features. Histological assessment remains the cornerstone of a PT diagnosis. However, recent genomic advancements have revealed the biological mechanisms underlying PTs, particularly malignant phyllodes tumors (MPTs). This comprehensive review integrates current genomic and molecular investigations that have elucidated the distinguishing features of PTs. Mutations in the MED12 gene represent early tumorigenic phenomena that are often observed in benign lesions, whereas modifications in the TERT promoter, alterations in TP53, and amplification of EGFR are associated with malignant transformation. Moreover, novel transcriptomic investigations have characterized discrete molecular subtypes exhibiting epithelial and fibrous attributes, thereby enriching our understanding of MPT heterogeneity. Actionable genomic modifications, including dysregulation of the PI3K/Akt/mTOR, MET, and IGF1R signaling cascades, represent promising directions for targeted therapeutic strategies; however, clinical validation is still insufficient. Advances in patient-derived models have created functional platforms conducive to drug screening and preclinical evaluation. Molecular examination has expanded our understanding of PTs, revealing the genomic components linked to malignant progression and identifying prospective therapeutic targets. Nevertheless, obstacles remain in the practical application of these discoveries, primarily owing to the intratumoral heterogeneity and rarity of MPTs. Future investigations should prioritize the integration of diverse omics methodologies, enhancement of preclinical testing frameworks, and establishment of global data-sharing initiatives to promote biomarker-driven treatment strategies.