{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T04:59:59Z","timestamp":1785387599387,"version":"3.55.0"},"reference-count":23,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Curr. Oncol.","Current Oncology"],"abstract":"<jats:p>Brain metastases in hormone receptor-positive metastatic breast cancer remain incompletely characterized at the molecular level. We report isolated central nervous system progression in a 60-year-old woman with hormone receptor-positive breast cancer initially diagnosed at the age of 38 and metastatic recurrence diagnosed at the age of 55. After approximately five years of extracranial disease control with letrozole plus palbociclib, she developed multiple brain metastases, including a large cerebellar lesion requiring surgical resection. Molecular profiling of the resected lesion identified ESR1 Y537S and ERBB2 Y772_A775dup, whereas postoperative plasma circulating tumor DNA analyzed using a sensitive next-generation sequencing assay showed no detectable somatic alteration. Extracranial disease remained in complete metabolic response. This tissue\u2013plasma discordance is compatible with spatial genomic heterogeneity but may also reflect a low circulating tumor fraction, postoperative reduction in tumor burden, and limited release of tumor-derived DNA from CNS lesions into the systemic circulation. This case highlights the limitations of plasma circulating tumor DNA for evaluating CNS-limited progression and supports direct molecular profiling of brain metastases when tissue is available.<\/jats:p>","DOI":"10.3390\/curroncol33080454","type":"journal-article","created":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T15:57:28Z","timestamp":1785254248000},"page":"454","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["ESR1 Y537S Detected in a Brain Metastasis but Not in Plasma ctDNA in HR+\/HER2-Low Metastatic Breast Cancer: A Case Report"],"prefix":"10.3390","volume":"33","author":[{"given":"Aem\u00e9lia","family":"N\u00e8gre","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Institute Paoli Calmettes, 13009 Marseille, France"},{"name":"Faculty of Medicine, Aix Marseille University, La Timone Campus, 13005 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lor\u00e8ne","family":"Seguin","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Institute Paoli Calmettes, 13009 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur","family":"G\u00e9raud Cremieux","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Institute Paoli Calmettes, 13009 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederic","family":"Viret","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Institute Paoli Calmettes, 13009 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agn\u00e8s","family":"Tallet","sequence":"additional","affiliation":[{"name":"Department of Radiotherapy, Institute Paoli Calmettes, CRCM, 13009 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8226-3127","authenticated-orcid":false,"given":"Cornel","family":"Popovici","sequence":"additional","affiliation":[{"name":"Cancer Biology Department, Institute Paoli Calmettes, 13009 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7570-7439","authenticated-orcid":false,"given":"Anthony","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Institute Paoli Calmettes, 13009 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6710-8284","authenticated-orcid":false,"given":"Alexandre","family":"de Nonneville","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Institute Paoli Calmettes, 13009 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1016\/S0002-9440(10)61180-7","article-title":"Breast Cancer Metastasis to the Central Nervous System","volume":"167","author":"Weil","year":"2005","journal-title":"Am. 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