Study in Leptomeningeal Metastases of Breast Cancer (LCS Bio Sein)

Cerebrospinal Fluid Biomarkers Value: Exploratory and Prospective Study in Leptomeningeal Metastases of Breast Cancer (LCS Bio Sein)

Breast cancer (BC) is the most frequent cause of leptomeningeal metastases (LM) .As for brain parenchymal metastases, the incidence of LM seems to be increasing, due to the growing incidence of metastatic BC, the improvement of survival and the poor diffusion of therapeutic agents into the central nervous system (CNS). Several prognostic factors have been identified, including the age at diagnosis, the functional and neurological status, the delay between the diagnosis of cancer and that of LM. The survival of patients is poor, less than 6 months in most published series. Several neuronal biomarkers could also be good candidates, such as the neurogranin CSF and/or serum levels or the CNS neurofilaments (NF), that seem to be a good reflect of axonal injury and neuronal loss. CNS NF have been investigated in several neurological diseases including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and multiple sclerosis, but not yet in CNS metastases. Indeed, the creation of a clinico-biological collection seems to be of high value in order to investigate future biomarkers of interest

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Biological: blood samples

Detailed Description

Breast cancer (BC) is the most frequent cause of leptomeningeal metastases (LM). As for brain parenchymal metastases, the incidence of LM seems to be increasing, due to the growing incidence of metastatic BC, the improvement of survival and the poor diffusion of therapeutic agents into the central nervous system (CNS). Several prognostic factors have been identified, including the age at diagnosis, the functional and neurological status, the delay between the diagnosis of cancer and that of LM. Other CSF biomarkers have been evaluated for the diagnosis of leptomeningeal metastases. Finally, the CellSearch® technique allows for the characterisation of proteins expressed by CSF tumors cells (E.G., HER2) and will make possible a better understanding of the physiopathology of tumor dissemination to the CS.

Other neuronal biomarkers could be interesting for the diagnosis of LM in BC patients. Among them, the protein Tau (total-Tau or T-Tau) is involved in several neurological diseases. However, to date, no study has evaluated CSF or serum T-Tau in LM from solid tumors.

Several neuronal biomarkers could also be good candidates, such as the neurogranin CSF and/or serum levels or the CNS neurofilaments (NF), that seem to be a good reflect of axonal injury and neuronal loss.

• Study Type: Interventional
• Enrollment (Actual): 51
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Montpellier, France, 34298
    • Institut régional du Cancer de Montpellier

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female patient ≥ 18 years-old, no age limit;
2. Histologically confirmed diagnosis of BC;
3. Hormone receptors and HER2 statuses of the primary tumor available;
4. Suspected LM based on clinical symptoms or signs, or radiological abnormalities;
5. Indication of diagnosis lumbar puncture decided by the oncologist in charge of the patient;
6. Patients must be affiliated to a Social Security System;
7. Patient information and written informed consent form signed prior to any study specific procedures.

Exclusion Criteria:

1. History of other cancer(s) than the BC (except completely resected non-melanoma skin cancer or successfully treated in situ carcinoma).
2. Hormone receptors and/or HER2 statuses of the primary tumor not available;
3. Patients with a medical contra-indication to the realization of a lumbar puncture;
4. Patients with psychological, family, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule;
5. Patients who are pregnant or breast-feeding.
6. Legal incapacity or limited legal capacity.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Biological samples; The CSF samples will be taken at the occasion of the first lumbar puncture performed for clinical purposes (suspected LM). If necessary for the routine diagnosis, a second and a third lumbar puncture will be performed according to the gold standard Two EDTA tubes (5 mL) and two dried tubes (5mL) will be will be taken the same day as the first lumbar puncture and transferred at ambient temperature to the Biological Resource Center of the ICM (Jean-Pierre Bleuse, Biobank number BB-0033-00059) to be processed within 1 hour Blood samples will be centrifuged at 3,000 g for 10 minutes at ambient temperature and will be aliquoted in 4 plasma and 4 serum aliquots and then stored at -80°C. Aliquots must be anonymized.

Biological: blood samples; Two EDTA tubes (5 mL) and two dried tubes (5mL) will be will be taken the same day as the first lumbar .

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity of the CellSearch® technique on CSF samples in comparison with the conventional cytology on one to three CSF sample	analysis of result with the 2 technical procedure	through study completion, an average of 2 years

Collaborators and Investigators

• Sponsor: Institut du Cancer de Montpellier - Val d'Aurelle
• Investigators: Study Director: marc ychou, Institut régional du Cancer de Montpellier

Publications and helpful links

General Publications

• Darlix A, Cayrefourcq L, Pouderoux S, Menjot de Champfleur N, Bievelez A, Jacot W, Leaha C, Thezenas S, Alix-Panabieres C. Detection of Circulating Tumor Cells in Cerebrospinal Fluid of Patients with Suspected Breast Cancer Leptomeningeal Metastases: A Prospective Study. Clin Chem. 2022 Oct 6;68(10):1311-1322. doi: 10.1093/clinchem/hvac127.
• Delaby C, Al Herk A, Hirtz C, Jacot W, Laigre M, Pouderoux S, Pradeilles N, Lehmann S, Darlix A. Hepcidin as an emerging predictor biomarker of leptomeningeal metastases in patients with metastatic breast cancer. BMC Cancer. 2025 Nov 21;25(1):1801. doi: 10.1186/s12885-025-15124-6.

Study record dates

Study Major Dates

• Study Start (Actual): January 6, 2017
• Primary Completion (Actual): February 3, 2020
• Study Completion (Actual): September 15, 2020

Study Registration Dates

• First Submitted: August 10, 2017
• First Submitted That Met QC Criteria: August 16, 2017
• First Posted (Actual): August 17, 2017

Study Record Updates

• Last Update Posted (Actual): March 12, 2026
• Last Update Submitted That Met QC Criteria: March 10, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Investigative Techniques; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Blood Specimen Collection
• Other Study ID Numbers: ICM-URC 2015/71

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No