Anlotinib-temozolomide combination achieves durable response in multimodal-resistant primary breast angiosarcoma with...

Primary breast angiosarcoma is an exceedingly rare malignancy with a high propensity for hematogenous metastasis, though skull base and dural involvement have never been reported. We present a 52-year-old woman diagnosed with stage IIA primary breast angiosarcoma (pT2N0M0) treated with mastectomy and adjuvant radiotherapy. Twenty-one months post-radiation therapy, she developed left orbital swelling and headache. Magnetic resonance imaging (MRI) revealed a 45×35-mm heterogeneously enhancing mass that extended from the skull base to the orbit with dural invasion, confirmed histologically as metastatic angiosarcoma. Following progression after radiotherapy and six cycles of anthracycline-based chemotherapy, salvage therapy combining anlotinib, a multi-target antiangiogenic tyrosine kinase inhibitor, and temozolomide, a blood-brain barrier-penetrant alkylating agent, was initiated. Within one week, her headache resolved, and three-month MRI demonstrated stable disease with resolution of temporalis enhancement and reduced dural thickening. The regimen was well-tolerated with no adverse events. At five-month follow-up, the patient remains progression-free. To our knowledge, this report describes the first documented case of skull base metastasis and dural involvement from primary breast angiosarcoma. The anlotinib-temozolomide combination achieved rapid symptomatic and radiographic control after multimodal therapy failure, suggesting synergistic efficacy against both angiogenesis and sanctuary-site disease. This report underscores the importance of targeting angiogenesis and leveraging central nervous system (CNS)-penetrating agents in angiosarcoma with atypical CNS dissemination, offering a novel therapeutic strategy for this aggressive malignancy.