Inclusion Criteria:

- Histologically confirmed breast cancer

- New diagnosis of leptomeningeal involvement confirmed by CSF cytology or clinical
signs and symptoms associated with MRI features

- Received first-line chemotherapy (in neoadjuvant or metastatic setting) co

- Age ≥ 18 ans

- Performance Status (ECOG) ≤ 2

- Life expectancy > 2 months

- Brain metastases allowed if asymptomatic

- study of CSF flux (isotopic method) if suspicion of CSF blockage, or after a local
radiotherapy for lifting blocking CSF to confirm absence of blocking CSF

- recovered from prior toxicities

- Adequate hematological, renal, hepatic parameters:

- Total bilirubin ≤ 3 ULN

- SGPT/ALT and SGOT/AST ≤ 2.5 ULN ; ≤ 5 ULN if hepatic metastases

- Effective contraceptive methods for non menopausal woman

- Patient covered by health insurance

- Informed consent form signed by the patient

Exclusion Criteria:

- leptomeningeal metastases other than from breast cancer

- prior cancer (> 5 years) except for cervix carcinoma, basocellular carcinoma, skin
spinocellular

- contre indication for MRI

- MRI : meningeal metastase > 1cm, obstruction of CSF

- contre indication for lumbar puncture, or for ventricular catheterization

- progressive brain metastases necessitating a radiotherapy

- prior cranio spinal radiotherapy

- prior intra tumoral treatment

- prior treatment with ARA-C or methotrexate

- concomitant treatment high dose methotrexate

- ventriculo peritoneal derivation

- active infection

- hypersensitivity for ARA-C or DepoCyte

- other severe or non controlled pathology

- patient already included in another therapeutic trial with experimental molecule (30
days prior first administration of DepoCyte ®)

- pregnancy or breast feeding woman

- unable to undergo medical follow up for geographic, social or psychological reasons