Evidence map›Paper›PMID 41883874›Full record

ArticleTherapeutic advances in medical oncology2026

Detection of actionable mutations in the cerebrospinal fluid and concordance/discordance with extracranial mutations in patients with metastatic breast cancer and leptomeningeal disease.

Laura A Huppert, Samantha Fisch, Lindy Her, Christine Hodgdon, Susie Brain, Carol Simmons, Andrew R Lai, Lev Malevanchik, Ronald Balassanian, Harish N Vasudevan and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Therapeutic advances in medical oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors.

Laura A HuppertDivision of Hematology and Oncology, Department of Medicine, University of California San Francisco, San Francisco, CA 94158, USA.ORCID https://orcid.org/0000-0002-8512-5608
Samantha FischDivision of Hematology and Oncology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
Lindy HerDivision of Hematology and Oncology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
Christine HodgdonGRASP Cancer, USA.
Susie BrainBreast Science Advocacy Core, Breast Oncology Program, University of California San Francisco, San Francisco, CA, USA.
Carol SimmonsBreast Science Advocacy Core, Breast Oncology Program, University of California San Francisco, San Francisco, CA, USA.
Andrew R LaiDivision of Hospital Medicine, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
Lev MalevanchikDivision of Hospital Medicine, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
Ronald BalassanianDivision of Pathology, University of California San Francisco, San Francisco, CA, USA.
Harish N VasudevanDivision of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.
Ramin MorshedDepartment of Neurosurgery, University of California San Francisco, San Francisco, CA, USA.
Steve BraunsteinDivision of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.
Lauren BoretaDivision of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.
Melanie MajureDivision of Hematology and Oncology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
A Jo ChienDivision of Hematology and Oncology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
Hope S RugoDivision of Breast Medical Oncology, Department of Medical Oncology and Therapeutics Research, City of Hope, Duarte, CA, USA.
Mark Jesus M MagbanuaDivision of Laboratory Medicine, University of California San Francisco, San Francisco, CA, USA.
Michelle E MeliskoDivision of Hematology and Oncology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.

Funding

UCSF Paul Calabresi K12 Career Development Program in Clinical OncologyK12CA260225 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BERGSLAND, EMILY K, BIVONA, TREVER G · 2021 to 2025
$2.6M
NCI NIH HHS K12 CA260225
6 · The paper itself

Abstract

Background: Leptomeningeal disease (LMD) is a devastating complication of metastatic breast cancer (MBC). Metastatic tumors to the central nervous system (CNS) are not routinely assessed for the presence of actionable mutations, hence the frequency and concordance of actionable mutations in the cerebrospinal fluid (CSF) versus extracranial sites are not well characterized. Objective: To evaluate the frequency and concordance of actionable mutations in the CSF versus extracranial sites in patients with MBC and LMD. Methods: In this single-center non-therapeutic prospective observational study, we enrolled 15 patients with MBC and known or suspected LMD from 2020 to 2024 and collected CSF, blood, and archival tumor samples. We enumerated CSF circulating tumor cells (CTCs) and analyzed circulating tumor DNA (ctDNA) via next-generation sequencing (NGS) using the CNSide technology (Biocept). When available, we compared CSF NGS results with available NGS data from matched blood and tumor samples. Results: Of the 15 patients enrolled, 14 were determined to have LMD based on CSF cytology, radiographic, and clinical assessment (7 hormone receptor-positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-), 6 triple negative breast cancer, 1 HER2+). CSF CTC enumeration was performed in a subset of patients and was positive in 5/7 (71.4%), of which 4/5 had negative CSF cytology. Median CTC enumeration was 0.29 CTCs/mL (range 0-136.4). Of the 14 patients with confirmed LMD, analysis of CSF ctDNA detected pathogenic variants in half of the patients (7/14, 50.0%). Comparison of CSF versus blood and/or tissue-based NGS testing was available for 10 patients: 5 patients (50%) had concordant CSF versus extracranial mutations, 3 patients (30%) had discordant CSF versus extracranial mutations, and 2 patients (20%) had both concordant and discordant CSF versus extracranial mutations. Conclusion: CSF CTCs can be detected and enumerated in patients with MBC and LMD, even in patients with negative CSF cytology. We were able to detect pathogenic mutations in the CSF ctDNA in half of the patients. We observed variable concordance and heterogeneity in the detection of actionable mutations between the CSF, blood, and tumor tissue, supporting the value of investigating the CSF to identify novel targets and resistance mechanisms. Larger studies are needed to assess the clinical utility of these observations, particularly with the development of novel targeted CNS-penetrant agents.

Indexed as

biomarker identificationbiomarkersbreast cancercirculating tumor cells (CTCs)circulating tumor DNA (ctDNA)

Identifiers

PMID41883874
PMCPMC13009763

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.