{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:10:52Z","timestamp":1753891852508,"version":"3.41.2"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T00:00:00Z","timestamp":1750291200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>Meningeal carcinomatosis (MC) is a distinct form of brain metastasis (BM) that occurs in patients with advanced triple-negative breast cancer (TNBC). The occurrence of BM typically indicates a poor prognosis. Spatial heterogeneity in HER2 expression is relatively common in breast cancer cases; however, the emergence of both temporal and spatial heterogeneity within the brain parenchyma and cerebrospinal fluid (CSF) is exceedingly rare. Thus, the phenomenon warrants further investigation. Herein, we report a case of advanced TNBC with BM and MC. HER2 was expressed in the CSF and exhibited spatial and temporal heterogeneity. The CSF was analyzed using immunohistochemistry and flow cytometry, confirming the presence of HER2-positive tumor cells in the patient\u2019s CSF. MC was effectively controlled after treatment with trastuzumab deruxtecan (T-DXd). Relevant literature was reviewed to analyze the reasons for this phenomenon. In this case, the spatial and temporal heterogeneity of the HER2 receptors observed in the CSF suggests that BM may be driven by the synergistic interaction of multiple subclonal tumor cells.<\/jats:p>","DOI":"10.3389\/fonc.2025.1599148","type":"journal-article","created":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T05:31:03Z","timestamp":1750311063000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: Triple-negative breast cancer with brain and meningeal metastases exhibits spatiotemporal heterogeneity in terms of HER2 expression"],"prefix":"10.3389","volume":"15","author":[{"given":"Xubin","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiyun","family":"Weng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,6,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1038\/s41379-020-00704-7","article-title":"Prognostic and predictive parameters in breast pathology: a pathologist\u2019s primer","volume":"34","author":"Allison","year":"2021","journal-title":"Mod Pathol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1038\/s41698-018-0055-0","article-title":"Recent advances in precision oncology research","volume":"2","author":"Bode","year":"2018","journal-title":"NPJ Precis Oncol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.25.9820","article-title":"Metastatic behavior of breast cancer subtypes","volume":"28","author":"Kennecke","year":"2010","journal-title":"J Clin Oncol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-013-1083-9","article-title":"The effect of tumor subtype on the time from primary diagnosis to development of brain metastases and survival in patients with breast cancer","volume":"112","author":"Sperduto","year":"2013","journal-title":"J Neurooncol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminoncol.2009.05.005","article-title":"Diagnostic tools for neoplastic meningitis: detecting disease, identifying patient risk, and determining benefit of treatment","volume":"36","author":"Chamberlain","year":"2009","journal-title":"Semin Oncol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/j.critrevonc.2019.01.020","article-title":"Leptomeningeal carcinomatosis in patients with breast cancer","volume":"135","author":"Franzoi","year":"2019","journal-title":"Crit Rev Oncol Hematol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-024-07339-1","article-title":"Demographic and clinical characteristics of patients with metastatic breast cancer and leptomeningeal disease: a single center retrospective cohort study","volume":"206","author":"Huppert","year":"2024","journal-title":"Breast Cancer Res Treat"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.lansea.2023.100331","article-title":"Treatment pattern and outcomes of leptomeningeal carcinomatosis in India - a retrospective study","volume":"24","author":"Goyal","year":"2024","journal-title":"Lancet Reg Health Southeast Asia"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(10)70034-6","article-title":"Intrathecal chemotherapy for treatment of leptomeningeal dissemination of metastatic tumours","volume":"11","author":"Beauchesne","year":"2010","journal-title":"Lancet Oncol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181dc1a69","article-title":"Leptomeningeal metastases in the MRI era","volume":"74","author":"Clarke","year":"2010","journal-title":"Neurology"},{"key":"B11","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1007\/s11060-020-03555-z","article-title":"Cerebrospinal fluid circulating tumor cells as a quantifiable measurement of leptomeningeal metastases in patients with HER2 positive cancer","volume":"148","author":"Malani","year":"2020","journal-title":"J Neurooncol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2019.00839","article-title":"Leptomeningeal metastasis: the role of cerebrospinal fluid diagnostics","volume":"10","author":"B\u00f6nig","year":"2019","journal-title":"Front Neurol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.jasc.2019.09.001","article-title":"Integration of rare cell capture technology into cytologic evaluation of cerebrospinal fluid specimens from patients with solid tumors and suspected leptomeningeal metastasis","volume":"9","author":"Torre","year":"2020","journal-title":"J Am Soc Cytopathol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.ccr-20-3954","article-title":"Detection of aneuploidy in cerebrospinal fluid from patients with breast cancer can improve diagnosis of leptomeningeal metastases","volume":"27","author":"Angus","year":"2021","journal-title":"Clin\u00a0Cancer Res."},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.ccr-21-3017","article-title":"Assessing CSF ctDNA to improve diagnostic accuracy and therapeutic monitoring in breast cancer leptomeningeal metastasis","volume":"28","author":"Fitzpatrick","year":"2022","journal-title":"Clin Cancer Res."},{"key":"B16","doi-asserted-by":"publisher","first-page":"5120","DOI":"10.1038\/s41467-020-18794-x","article-title":"Concepts of extracellular matrix remodelling in tumour progression and metastasis","volume":"11","author":"Winkler","year":"2020","journal-title":"Nat Commun."},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2023.102521","article-title":"Molecular aspects of brain metastases in breast cancer","volume":"114","author":"Tomasik","year":"2023","journal-title":"Cancer Treat Rev"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-024-00700-y","article-title":"The path to leptomeningeal metastasis","volume":"24","author":"Remsik","year":"2024","journal-title":"Nat Rev Cancer."},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1126\/science.adh5548","article-title":"Breast cancer exploits neural signaling pathways for bone-to-meninges metastasis","volume":"384","author":"Whiteley","year":"2024","journal-title":"Science."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1101","DOI":"10.1016\/j.cell.2017.02.025","article-title":"Complement component 3 adapts the cerebrospinal fluid for leptomeningeal metastasis","volume":"168","author":"Boire","year":"2017","journal-title":"Cell"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaz2193","article-title":"Cancer cells deploy lipocalin-2 to collect limiting iron in leptomeningeal metastasis","volume":"369","author":"Chi","year":"2020","journal-title":"Science."},{"key":"B22","doi-asserted-by":"publisher","first-page":"e1236","DOI":"10.1002\/cnr2.1236","article-title":"Leptomeningeal metastatic cells adopt two phenotypic states","volume":"5","author":"Remsik","year":"2022","journal-title":"Cancer Rep (Hoboken)."},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noaa025","article-title":"Estrogen\/progesterone receptor and HER2 discordance between primary tumor and brain metastases in breast cancer and its effect on treatment and survival","volume":"22","author":"Sperduto","year":"2020","journal-title":"Neuro Oncol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noaa013","article-title":"Subtype switching in breast cancer brain metastases: a multicenter analysis","volume":"22","author":"Hulsbergen","year":"2020","journal-title":"Neuro Oncol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1126\/science.1235122","article-title":"Cancer genome landscapes","volume":"339","author":"Vogelstein","year":"2013","journal-title":"Science"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.04.024","article-title":"Mutational processes molding the genomes of 21 breast cancers","volume":"149","author":"Nik-Zainal","year":"2012","journal-title":"Cell"},{"key":"B27","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1186\/s12935-024-03538-4","article-title":"Life history dynamics of evolving tumors: insights into task specialization, trade-offs, and tumor heterogeneity","volume":"24","author":"Ahmed","year":"2024","journal-title":"Cancer Cell Int"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2012.36","article-title":"Intratumoral heterogeneity of HER2 gene amplification in breast cancer: its clinicopathological significance","volume":"25","author":"Seol","year":"2012","journal-title":"Mod Pathol"},{"key":"B29","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1007\/s10549-016-3856-2","article-title":"HER2 intratumoral heterogeneity analyses by concurrent HER2 gene and protein assessment for the prognosis of HER2 negative invasive breast cancer patients","volume":"158","author":"Kurozumi","year":"2016","journal-title":"Breast Cancer Res Treat"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1007\/s00795-024-00386-z","article-title":"Utility of human epidermal growth factor 2 heterogeneity as a prognostic factor in triple-negative breast cancer","volume":"57","author":"Narusawa","year":"2024","journal-title":"Med Mol Morphol"},{"key":"B31","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1186\/s12916-017-0900-y","article-title":"The role of tumour heterogeneity and clonal cooperativity in metastasis, immune evasion and clinical outcome","volume":"15","author":"Caswell","year":"2017","journal-title":"BMC Med"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3261","article-title":"Intra-tumour heterogeneity: a looking glass for cancer","volume":"12","author":"Marusyk","year":"2012","journal-title":"Nat Rev Cancer"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2627","article-title":"Parallel progression of primary tumours and metastases","volume":"9","author":"Klein","year":"2009","journal-title":"Nat Rev Cancer"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1038\/nrc.2017.126","article-title":"Genetic insights into the morass of metastatic heterogeneity","volume":"18","author":"Hunter","year":"2018","journal-title":"Nat Rev Cancer"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2025.1599148\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T05:31:04Z","timestamp":1750311064000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2025.1599148\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,19]]},"references-count":34,"alternative-id":["10.3389\/fonc.2025.1599148"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2025.1599148","relation":{},"ISSN":["2234-943X"],"issn-type":[{"type":"electronic","value":"2234-943X"}],"subject":[],"published":{"date-parts":[[2025,6,19]]},"article-number":"1599148"}}