Clinical outcomes and genomic alterations in patients with metastatic malignant phyllodes tumors

Background: Malignant phyllodes tumors (MPTs) are rare fibroepithelial breast tumors with no standard treatment for metastatic or recurrent cases. Comprehensive genomic profiling (CGP) has been conducted for MPT; however, its association with treatment remains unclear. Methods: A retrospective study was conducted on patients with advanced or recurrent MPTs treated with chemotherapy between 2013 and 2022 at two hospitals, analyzing clinical data, CGP, treatment outcomes, and survival. Results: Five patients with metastatic MPTs who had received chemotherapy were identified. The median age was 55 years (range, 50–66), and all patients were female. As first-line treatment, four patients received doxorubicin plus ifosfamide (AI) combination therapy, while one received doxorubicin monotherapy. Among those treated with AI therapy, the best responses were partial response in three patients and stable disease in one. The median progression-free survival (PFS) for patients treated with AI therapy was 5.3 months. Of the five patients two proceeded to second-line therapy, and one patient received up to fourth-line treatment. Next-generation sequencing-based CGP testing was performed in four cases. One patient with an FGFR1-N546K-mutated MPT achieved a relatively long PFS of 6.8 months with pazopanib therapy, a multi-kinase inhibitor targeting FGFR1 among other kinases, as fourth-line therapy. Conclusion: AI therapy is useful for advanced or recurrent MPTs. The observed clinical benefit of pazopanib in a patient with FGFR1 N546Kmutated MPT suggests that FGFR1 kinase domain mutations may be a relevant factor in responsiveness of FGFR1-targeted therapy. Further data accumulation is warranted.