{ "abstract": "Background: Invasive lobular carcinoma (ILC) is known to exhibit distinct metastatic patterns compared with carcinoma of no special type (NST); however, little is known about its specific propensity for central nervous system (CNS) and leptomeningeal (LM) involvement, particularly in estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative subtype.\n\nPatients and methods: We leveraged a multicenter study of 1710 patients with advanced breast cancer (BC). We recorded site of first metastatic recurrence and occurrence/type of the first CNS event. The study endpoints were CNS-free survival, LM-free survival, and post-LM survival. The risk of LM as the first CNS event across histological types was evaluated using a competing-risk framework.\n\nResults: Among 1587 patients with known tumor histology, 15.5% had ILC. Within the ER-positive/HER2-negative BC cohort (n = 669), 31.5% of patients developed a CNS event. ILC and NST were associated with similar metastatic CNS-free survival [hazard ratio (HR) 1.30, 95% confidence interval (CI) 0.95-1.77, P = 0.095]. In contrast, metastatic LM-free survival was significantly and independently shorter in ILC versus NST (multivariate analysis of LM events without concurrent brain metastases, adjusted HR 4.94, 95% CI 1.57-15.83, P = 0.006). Consistently, Fine-Gray competing-risk analysis confirmed a significantly higher risk of LM involvement as the first CNS event for ILC versus NST (adjusted subdistribution hazard ratio 5.07, 95% CI 1.57-16.41, P = 0.007). Among patients with ER-positive/HER2-negative BC and LM disease, ILC was associated with worse post-LM survival compared with NST (HR 2.79, 95% CI 1.03-4.17, P = 0.040). In patients with ILC presenting with extracranial metastatic disease, we observed similar LM-free survival between those treated with cyclin-dependent kinase 4 and 6 inhibitors and those who were not (P = 0.286).\n\nConclusions: In patients with ER-positive/HER2-negative advanced BC, ILC was independently associated with a higher cumulative incidence of LM as the first CNS event than NST. Patients with ILC who developed LM also experienced poorer post-LM survival. These findings highlight the need for heightened clinical awareness and support prospective studies evaluating earlier LM detection in this population.", "abstract_shown": true, "affiliations": [ "Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy", "Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy", "Oncology 2 Division, Istituto Oncologico Veneto IRCCS, Padova, Italy", "Oncology and Hematology-Oncology Department, School of Medicine, University of Milan, Milan, Italy", "Department of Medical and Surgical Sciences for Children and Adults, University Hospital of Modena, Modena, Italy", "Department of Pathology and Molecular Genetics, Treviso General Hospital, Treviso, Italy", "Department of Radiological, Oncological and Pathological Science, Sapienza University of Rome, Rome, Italy", "Medical Oncology Unit, Ca’ Foncello Hospital, Treviso, Italy", "Institute of Anatomic Pathology, Padua University-Hospital, Padova, Italy" ], "article_type": "research article", "arxiv": null, "author_total": 20, "authors": [ { "affs": [ 0 ], "name": "F. Miglietta" }, { "affs": [ 1 ], "name": "C. Vernieri" }, { "affs": [ 2 ], "name": "T. Giarratano" }, { "affs": [ 0 ], "name": "G. Griguolo" }, { "affs": [ 0 ], "name": "M. Bottosso" }, { "affs": [ 3 ], "name": "A. Vingiani" }, { "affs": [ 4 ], "name": "F. Piacentini" }, { "affs": [ 5 ], "name": "M. Cacciatore" }, { "affs": [ 6 ], "name": "A. Botticelli" }, { "affs": [ 1 ], "name": "G. Fotia" }, { "affs": [ 0 ], "name": "P. Napolitano" }, { "affs": [ 0 ], "name": "G. Landa" }, { "affs": [ 2 ], "name": "G.M. Vernaci" }, { "affs": [ 2 ], "name": "E. Di Liso" }, { "affs": [ 4 ], "name": "L. Casadei" }, { "affs": [ 7 ], "name": "D. Palleschi" }, { "affs": [ 3 ], "name": "G. Pruneri" }, { "affs": [ 8 ], "name": "A.P. Dei Tos" }, { "affs": [ 0 ], "name": "V. Guarneri" }, { "affs": [ 0 ], "name": "M.V. Dieci" } ], "bibtex": "https://research.draconitic.com/paper/4msaktz0tg3x6.bib", "cited_by": 0, "doi": "10.1016/j.esmoop.2026.108550", "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13718780/?tool=EBI", "id": "4msaktz0tg3x6", "issns": [ "2059-7029" ], "landing_url": "https://europepmc.org/article/PMC/PMC13718780", "language": "eng", "licence": "CC-BY-NC-ND", "licence_label": "CC BY-NC-ND", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/", "metadata_licence": null, "native_subjects": [ [ "heading", "Original Article" ], [ "openalex", "2740|Brain Metastases and Treatment" ] ], "openalex": "W7223097862", "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13718780/pdf/?tool=EBI", "pmcid": "PMC13718780", "pmid": "42906524", "published": "2026-10-21", "publisher": "Elsevier", "ris": "https://research.draconitic.com/paper/4msaktz0tg3x6.ris", "sources": [ { "first_seen": "2026-10-31T00:20:38Z", "native_id": "PMC:PMC13718780", "source": "europepmc", "url": "https://europepmc.org/article/PMC/PMC13718780" }, { "first_seen": "2026-11-02T12:22:44Z", "native_id": "PMC13718780", "source": "pmc", "url": "https://doi.org/10.1016/j.esmoop.2026.108550" } ], "subjects": [ { "field": "medicine", "origin": "openalex:2740|Brain Metastases and Treatment", "subfield": "general" } ], "title": "Patterns of central nervous system and leptomeningeal involvement in advanced breast cancer with invasive lobular histology: a large multicenter study with a focus on estrogen receptor-positive/HER2-negative disease", "title_text": "Patterns of central nervous system and leptomeningeal involvement in advanced breast cancer with invasive lobular histology: a large multicenter study with a focus on estrogen receptor-positive/HER2-negative disease", "type": "peer-reviewed", "updated_at": "2026-11-02T12:22:44Z", "url": "https://research.draconitic.com/paper/4msaktz0tg3x6", "venue": "ESMO open", "versions": [] }