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. 2025 Jun:81:104433.
doi: 10.1016/j.breast.2025.104433. Epub 2025 Mar 28.

Clinical characteristics and prognostic factors in patients with breast cancer and leptomeningeal metastases from a large registry of BMBC

Elena Laakmann  1 , Marcus Schmidt  2 , Kristina Lübbe  3 , Elisa Agostinetto  4 , Mette van Ramshorst  5 , Thomas Decker  6 , Wolfram Malter  7 , Francesco Schettini  8 , Mario Fontes Sousa  9 , Carsten Denkert  10 , Tanja Neunhöffer  11 , Leonor Matos  12 , Sabine Linn  5 , Marc Thill  13 , Rudolf Weide  14 , Amanda Fitzpatrick  15 , Marta Vaz Batista  16 , Christoph Mundhenke  17 , Tjoung-Won Park-Simon  18 , Fanny Le Du  19 , Kerstin Riecke  20 , Tanja Fehm  21 , Isabel Witzel  22 , Julia Rey  23 , Valentina Nekljudova  23 , Sibylle Loibl  23 , Volkmar Müller  20
Affiliations

Clinical characteristics and prognostic factors in patients with breast cancer and leptomeningeal metastases from a large registry of BMBC

Elena Laakmann et al. Breast. 2025 Jun.

Abstract

Background: Leptomeningeal metastases (LM) in patients with breast cancer (BC) are associated with a dismal prognosis. We explored clinical characteristics and prognostic factors in patients with BC and LM in the German Brain Metastases in Breast Cancer Registry.

Methods: All patients with histologically confirmed BC and diagnosis of LM (defined as the presence of tumor cells in the cerebrospinal fluid, or presence of typical clinical symptoms in combination with typical magnetic resonance imaging findings) were included.

Results: A total of 3857 patients were included in the analysis (n = 859 (22.3 %) with LM). Among patients with LM a median progression-free survival was 4.2 months (95 % CI 3.6-4.8), and median overall survival was 5.7 months (95 % CI 4.9-6.7). In the multivariate analysis older age ( ≥ 60 vs. <60 years, Hazard ratio (HR): 1.65, 95 %CI: 1.25-2.18), worse performance status (ECOG 2-4 vs. 0-1 HR: 2.15, 95 %CI: 1.63-2.82), hormone receptor positive/HER2-negative (HR+/HER2-) or triple-negative subtype (HR: 1.54 95CI%: 1.07-2.23 and HR: 1.87, 95 %CI: 1.25-2.81), and higher number of BM (2-3 vs. 1, HR: 1.49, 95 %CI: 1.05-2.11 4) were significantly associated with a higher risk of death. Stereotactic radiotherapy (HR 0.49 95 %CI 0.30-0.79) and whole brain irradiation (HR: 0.58, 95 %CI: 0.42-0.80), endocrine therapy in patients with HR + BC (HR: 0.31, 95 %CI: 0.21-0.45) as well as HER2-targeted therapy for patients with HER2+ BC (HR 0.41, 95 %CI: 0.25-0.68) were associated with a significantly longer survival.

Conclusions: Clinicopathological factors associated with survival can help clinicians identify patients who are candidates for treatment (de)escalation in clinical trials.

Keywords: Breast cancer; Leptomeningeal metastasis; Registry.

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Conflict of interest statement

Declaration of competing interest EA: Honoraria from: Eli Lilly, Sandoz, AstraZeneca, Novartis; Advisory Board for AstraZeneca; Research grant to my Institution from Gilead; Support for attending medical conferences from: Novartis, Roche, Eli Lilly, Genetic, Istituto Gentili, Daiichi Sankyo, AstraZeneca (all outside this manuscript). LM: reports speaking fee/honoraria from AstraZeneca, Roche, Lilly, Novartis, Daiichi Sankyo; consultancy role for Grunenthal and Novartis; meeting/travel grants from Lilly, Pfizer, Novartis and Daichii Sankyo. FS: declares personal fees for educational events and/or materials from Gilead, Daiichy Sankyo and Novartis; travel expenses from Gilead, Daiichy Sankyo and Novartis; advisory fees from Pfizer. JR and VN declares to be GBG Forschungs GmbH employee. GBG Forschungs GmbH received funding for research grants from Abbvie, Amgen, AstraZeneca, BMS, Daiichi-Sankyo, Gilead, Molecular Health, Stemline Menarini, Celgene/BMS, Novartis, Pfizer and Roche (paid to the institution). GBG Forschungs GmbH has licensing fees from VMscope GmbH. In addition, GBG Forschungs GmbH has a patent EP21152186.9 pending, a patent EP19808852.8 pending, and a patent EP14153692.0 pending. EL reports travel expenses from Pierre Fabre, honoraria for educational events from Astra Zeneca, Seagen and advisory board fees from Novartis, Astra Zeneca and Daiichi Sankyo (all outside this manuscript). AF, MvR, RW: no relevant disclosures to declare. MS reports personal fees from AstraZeneca, BioNTech, Daiichi Sankyo, Eisai, Exact Sciences, GILEAD, Lilly, Menarini-Stemline, Molecular Health, MSD, Novartis, Pantarhei Bioscience, Pfizer, Pierre Fabre, Roche, and SeaGen, His institution has received research funding from AstraZeneca, BioNTech, Eisai, Genentech, German Breast Group, Novartis, Palleos, Pantarhei Bioscience, Pierre Fabre, and SeaGen. In addition, he has a patent for EP 2390370 B1 and a patent for EP 2951317 B1 issued. TF received travel expenses from Daichii Sankyo and Roche, honoraria from Onkowissen, FOMF, Medcocept IW received honoraria from Astra Zeneca, GSK, Lilly, Novartis, Roche, Seagen, Pfizer, Daiichi Sankyo and Gilead. MT reports honoraria für advisory board from Agendia, Amgen, AstraZeneca, Aurikamed, Becton/Dickinson, ClearCut, Daiichi Sankyo, Eisai, Exact Sciences, Gilead Science, GSK, Lilly, MSD, Neodynamics, Novartis, Onkowissen, Organon, Pfizer, pfm Medical, Pierre-Fabre, Roche, Seagen, Sirius Medical, Sysmex, manuscript support from Amgen, ClearCut, pfm medical, Roche, Servier, reimbursement of travel expenses from Amgen, Art Tempi, AstraZeneca, Clearcut, Daiichi Sankyo, Eisai, Exact Sciences, Gilead, Hexal, I-Med-Institute, Lilly, MSD, Neodynamics, Novartis, Pfizer, pfm Medical, Roche, RTI Surgical, Seagen, ZP Therapeutics, congress support from Amgen, AstraZeneca, Daiichi Sanyko, Gilead, Hexal, Lilly, Neodynamics, Novartis, Pfizer, Pierre Fabre, Roche, Sirius Medical, moreover honoraria for lectures from Agendia, Amgen, Art Tempi, AstraZeneca, Eisai, Exact Sciences, Gilead Science, GSK, Hexal, I-Med-Institute, Jörg Eickeler, Laborarztpraxis Walther et al., Lilly, Medscape, MSD, Novartis, Onkowissen, Pfizer, pfm medical, Roche, Seagen, StreamedUp, Stemline, Sysmex, Vifor, Viatris, ZP Therapeutics, institutional trial funding from Endomag, Exact Sciences and institutional trial honoraria from AstraZeneca, Biom’Up, CairnSurgical, Clearcut, Neodynamics, Novartis, pfm medical, Roche, RTI Surgical. FLD: Consultancy fee or honoraria: Eli Lilly, Pfizer, Novartis, Seagen, Daiichi, AstraZeneca, Exact sciences. Research grant to my Institution from Daiichi. Support for attending medical conferences from: Novartis, Roche, Eli Lilly, Pfizer, Daiichi Sankyo, AstraZeneca (all outside the submitted work). C. Mundhenke reports personal fees from AstraZeneca, Daiichi Sankyo, Eisai, Menarini-Stemline, MSD, Novartis, Pfizer and SeaGen. VM Speaker honoraria: Astra Zeneca, Daiichi-Sankyo, Eisai, Pfizer, MSD, Medac, Novartis, Roche, Seagen, Onkowissen, high5 Oncology, Medscape, Gilead, Pierre Fabre, iMED Institut. Consultancy honoraria: Roche, Pierre Fabre, PINK, ClinSol, Novartis, MSD, Daiichi-Sankyo, Eisai, Lilly, Seagen, Gilead, Stemline, Institutional research support: Novartis, Roche, Seagen, Genentech, Astra Zeneca, Travel grants: Astra Zeneca, Roche, Pfizer, Daiichi Sankyo, Gilead. Given his role as specialty editor (medical oncology) of The Breast Journal, Volkmar Mueller had no involvement in the peer-review of this article and has no involvement in the peer review of this article and has no access to information regarding its peer review.

Figures

Fig. 1
Fig. 1
Distribution of patients with and without LM in the BMBC registry. Legend: BM: brain metastases, LM: leptomeningeal metastases.
Fig. 2
Fig. 2
A: Progression-free survival in patients with vs. without leptomeningeal metastases. B: Overall survival of patients with vs. without leptomeningeal disease. Legend. LM: leptomeningeal metastasis; BM: brain metastasis; HR: hazard ratio for progression-free survival; CI: confidence interval.
See this image and copyright information in PMC

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