Analyses of Exosomes in the Cerebrospinal Fluid for Breast Cancer Patients With Suspicion of Leptomeningeal Metastasis.

Study Overview
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Brief Summary
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This is a multicenter, interventional, prospective study among breast cancer patients with a suspicion of metastatic meningitis. The current study aims to assess the use of proteomic profile issued from cerebrospinal fluid microvesicles for diagnosis of leptomeningeal metastases.

Detailed Description
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The aim of this study is to describe the association between the initial proteomic profile issued from cerebrospinal fluid microvesicles and the initial cytological analysis of the cerebrospinal fluid in breast cancer patients with a suspicion of metastatic meningitis. Other objectives of the study include: Describing the association between the initial proteomic profile and: the histological types and hormonal receptors status of the breast cancer, the likelihood of leptomeningeal metastasis according to the EANO-ESMO classification (Lack of evidence / possible / probable / confirmed) , the likelihood of leptomeningeal metastasis according to the EANO-ESMO classification, combined with histological type and hormonal receptors status. Evaluate the prognostic value of the proteomic profiling for overall survival, according to the EANO-ESMO classification and other known prognosis factors, in patients classified possible, probable or confirmed leading to leptomeningeal metastases specific treatment, Evaluate the impact of the evolution of the proteomic profile a month after the start of this treatment on the overall survival, in patients with leptomeningeal metastases specific treatment, Evaluate the association between the proteomic profile and the EANO-ESMO classification at least 3 months after the initial EANO-ESMO classification, Evaluate the evolution of the proteomic profile 3 months after the initial EANO-ESMO classification, in patients initially classified lack of evidence, broadly and according to the evolution of cytology, the administered treatments and to the EANO-ESMO response if applicable, Compare the proteomic profiles issued from cerebrospinal fluid and blood

Official Title
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Benefit of Analyzing Exosomes in the Cerebrospinal Fluid During the Medical Care of Breast Cancer Patients With Suspicion of Leptomeningeal Metastasis.

Conditions
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Leptomeningeal Metastasis, Breast Cancer

Intervention / Treatment
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* Procedure: Cerebrospinal fluid and blood sample collection at the initial diagnostic assessment
* Procedure: Cerebrospinal fluid and blood sample collection if conclusions of initial diagnostic assessment are Lack of evidence according to EANO-ESMO classification
* Procedure: Cerebrospinal fluid and blood sample collection if conclusions of initial diagnostic assessment are confirmed, probable or possible, leading to leptomeningeal metastase specific treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient with histologically proven breast cancer Patient with suspected metastatic leptomeningitis Age ≥ 18 years Patient covered by the French social security regime Signed written informed consent Exclusion Criteria: History of cancer other than the one being treated Contraindication to carrying out the lumbar puncture or cerebrospinal MRI Pregnant or breastfeeding patient

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cerebrospinal fluid and Blood sample collection<br>Collection of cerebrospinal fluid and blood samples: At initial diagnostic assessment; 1 month and 3 months after initial diagnostic assessment, for patients classified possible, probable or confirmed according to EANO-ESMO classification, leading to specific leptomeningeal metastase treatment; In case of symptoms leading to leptomeningeal metastase suspicion and at least 3 months after diagnostic assessment, for patients classified lack of evidence according to EANO-ESMO classification. | Procedure: Cerebrospinal fluid and blood sample collection at the initial diagnostic assessment<br>* At the initial diagnostic assessment, 3mL of cerebrospinal fluid and 10 ml of blood sample will be collected in order to determine the proteomic profile. Cerebrospinal fluid will be collected during a lumbar puncture aiming to diagnose leptomeningeal metastases.<br>Procedure: Cerebrospinal fluid and blood sample collection if conclusions of initial diagnostic assessment are Lack of evidence according to EANO-ESMO classification<br>* 3mL of cerebrospinal fluid and 10 ml of blood sample will be collected: When suspected metastatic meningitis symptoms arise and at least 3 months after the initial diagnostic assessment, In order to determine the proteomic profile. Cerebrospinal fluid will be collected during a lumbar puncture aiming to diagnose leptomeningeal metastases.<br>Procedure: Cerebrospinal fluid and blood sample collection if conclusions of initial diagnostic assessment are confirmed, probable or possible, leading to leptomeningeal metastase specific treatment<br>* 3mL of cerebrospinal fluid and 10 ml of blood sample will be collected: 1 month after the beginning of the specific treatment, 3 months after the beginning of the specific treatment. Cerebrospinal fluid will be collected during a lumbar puncture aiming to assess treatment response or at intrathecal injection of treatment.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proteomic profiles issued from cerebrospinal fluid at diagnosis | Proteomic profile will be obtained by bioinformatic analysis of cerebrospinal fluid. | Up to 1 week | 
| Cytology of cerebrospinal fluid at diagnosis | Results of cytological analysis of cerebrospinal fluid will be Positive, negative, equivocal. | Up to 1 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proteomic profiles issued from cerebrospinal fluid | Proteomic profile will be obtained by bioinformatic analysis of cerebrospinal fluid: 1 month and 3 month after the start of a specific treatment of the leptomeningeal metastasis, if applicable, 3 months after the initial diagnosis of leptomeningeal metastasis if the likehood of leptomeningeal metastasis is lack of evidence. | Up to 3 months | 
| Histological subtype | Histological subtype will be subdivised as invasive ductal breast carcinoma, invasive lobular breast carcinoma, other brest carcinoma. | Before registration in study | 
| Hormonal receptors status | Hormonal receptors status will be subdivised as: Positive hormonal receptors / Positive HER2 Positive hormonal receptors / Negative HER2 Negative hormonal receptors / Positive HER2 Triple negative | Before registration in study | 
| Likehood of leptomeningeal metastasis according to the EANO-ESMO classification. | EANO-ESMO classification is obtained by searching clinical symptoms, cancer cells in the cerebrospinal fluid (obtained by lumbar puncture), signs in RMI. The likehood of leptomeningeal metastasis is: Lack of evidence, Possible, Probable, Confirmed. | Up to 3 months after the intial diagnosis | 
| Overall survival | Overall survival is defined as time from date of registration to date of death regardless of the cause. | Time from date of registration to date of death regardless of the cause, assessed up to 1 year | 
| Proteomic profiles issued from blood | Proteomic profile will be obtained by bioinformatic analysis of blood. | Up to 3 months after the intial diagnosis | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cerebrospinal fluid, Proteomic profile