{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T04:48:10Z","timestamp":1777265290167,"version":"3.51.4"},"reference-count":19,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T00:00:00Z","timestamp":1777248000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>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\u00d735-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.<\/jats:p>","DOI":"10.3389\/fonc.2026.1619754","type":"journal-article","created":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T04:27:53Z","timestamp":1777264073000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Anlotinib-temozolomide combination achieves durable response in multimodal-resistant primary breast angiosarcoma with skull base metastasis and dural involvement: a case report"],"prefix":"10.3389","volume":"16","author":[{"given":"Shujie","family":"Song","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University","place":["Yantai, Shandong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weiyi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University","place":["Yantai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xixi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University","place":["Yantai, Shandong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongxia","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Radiology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University","place":["Yantai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanchun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University","place":["Yantai, Shandong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(10)70023-1","article-title":"Angiosarcoma","volume":"11","author":"Young","year":"2010","journal-title":"Lancet Oncol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdm381","article-title":"Angiosarcomas, a heterogeneous group of sarcomas with specific behavior depending on primary site: a retrospective study of 161 cases","volume":"18","author":"Fayette","year":"2007","journal-title":"Ann Oncol Off J Eur Soc Med Oncol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1097\/SLA.0b013e3181dbb75a","article-title":"Angiosarcoma: clinical and molecular insights","volume":"251","author":"Lahat","year":"2010","journal-title":"Ann Surg"},{"key":"B4","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1111\/j.1365-2559.2007.02892.x","article-title":"Vascular proliferations of the breast","volume":"52","author":"Brodie","year":"2008","journal-title":"Histopathology"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3747\/co.25.3816","article-title":"Primary angiosarcoma of the breast-series of 11 consecutive cases-a single-centre experience","volume":"25","author":"Kunkiel","year":"2018","journal-title":"Curr Oncol Tor Ont"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.22784","article-title":"Primary angiosarcomas of the breast","volume":"110","author":"Sher","year":"2007","journal-title":"Cancer"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.17.3146","article-title":"Phase II trial of weekly paclitaxel for unresectable angiosarcoma: the ANGIOTAX Study","volume":"26","author":"Penel","year":"2008","journal-title":"J Clin Oncol Off J Am Soc Clin Oncol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"778","DOI":"10.1186\/s12885-020-07300-7","article-title":"Survival predictors of metastatic angiosarcomas: a surveillance, epidemiology, and end results program population-based retrospective study","volume":"20","author":"Ren","year":"2020","journal-title":"BMC Cancer"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3816\/CBC.2007.n.045","article-title":"Angiosarcoma arising in an unirradiated breast with subsequent pituitary metastasis","volume":"7","author":"Rozen","year":"2007","journal-title":"Clin Breast Cancer"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-020-0511-6","article-title":"Primary mammary angiosarcomas harbor frequent mutations in KDR and PIK3CA and show evidence of distinct pathogenesis","volume":"33","author":"Beca","year":"2020","journal-title":"Mod Pathol Off J U S Can Acad Pathol Inc"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2019.04.010","article-title":"Targeting angiosarcomas of the soft tissues: a challenging effort in a heterogeneous and rare disease","volume":"138","author":"Weidema","year":"2019","journal-title":"Crit Rev Oncol Hematol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2011-0237","article-title":"Sorafenib for patients with advanced angiosarcoma: a phase II trial from the French Sarcoma Group (GSF\/GETO)","volume":"17","author":"Ray-Coquard","year":"2012","journal-title":"Oncologist"},{"key":"B13","doi-asserted-by":"publisher","first-page":"963","DOI":"10.1186\/s12885-018-4828-1","article-title":"Prognostic and predictive factors for angiosarcoma patients receiving paclitaxel once weekly plus or minus bevacizumab: an ancillary study derived from a randomized clinical trial","volume":"18","author":"Lebellec","year":"2018","journal-title":"BMC Cancer"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-17-3766","article-title":"Safety and efficacy of anlotinib, a multikinase angiogenesis inhibitor, in patients with refractory metastatic soft-tissue sarcoma","volume":"24","author":"Chi","year":"2018","journal-title":"Clin Cancer Res Off J Am Assoc Cancer Res"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1172\/JCI15451","article-title":"Transport of paclitaxel (Taxol) across the blood-brain barrier in vitro and in vivo","volume":"110","author":"Fellner","year":"2002","journal-title":"J Clin Invest"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa043330","article-title":"Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma","volume":"352","author":"Stupp","year":"2005","journal-title":"N Engl J Med"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-23-0388","article-title":"Safety and efficacy of anlotinib hydrochloride plus temozolomide in patients with recurrent glioblastoma","volume":"29","author":"Xu","year":"2023","journal-title":"Clin Cancer Res Off J Am Assoc Cancer Res"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1623","DOI":"10.1186\/s12885-025-15123-7","article-title":"A retrospective study of 30 cases evaluating the efficacy and safety of anlotinib plus temozolomide for recurrent\/residual glioma from a single center","volume":"25","author":"Xu","year":"2025","journal-title":"BMC Cancer"},{"key":"B19","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1007\/s12672-025-02118-w","article-title":"Nomogram construction for overall survival in breast angiosarcoma based on clinicopathological features: a population-based cohort study","volume":"16","author":"Ding","year":"2025","journal-title":"Discov Oncol"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1619754\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T04:27:54Z","timestamp":1777264074000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1619754\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,27]]},"references-count":19,"alternative-id":["10.3389\/fonc.2026.1619754"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2026.1619754","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,27]]},"article-number":"1619754"}}