Intrapleural Bevacizumab After Pleural Drainage in the Context of Breast Cancer

Inclusion Criteria:

1. Patient with histologically documented pleural effusion in a type of breast carcinoma in exudate or with no other identified cause. In the absence of positive cytology, will ensure that there is no other cause of the patient's history may explain the effusion.
2. Unilateral or bilateral malignant pleural effusion but requiring drainage on only one side.
3. Patient presenting an indication for pleural implantable device, means that requiring at least one pleural drainage.
4. Patient aged 18 years old or more and without measure of legal protection
5. Subject female or male
6. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤ 2
7. Expected life span \> 2 months
8. Corticosteroids authorized if started less than 15 days before enrollment and no dose modification will be allowed during treatment
9. Adequate biological functions 14 days before inclusion:

   * Haemoglobin ≥ 8 g/dl (transfusion authorized)
   * Neutrophil count (ANC) ≥ 1000/mm3
   * Platelet count ≥ 100 000/mm3
   * International Normalized Ratio (INR) ≤ 1.5 and/or Prothrombin Ratio (TR) ≥ 70 % and Partial Thromboplastin Time (PTT) ≤ 1.5
   * Aspartate Aminotransferase Test (AST), Alanine Aminotransferase Test (ALT), Gamma-Glutamyl Transpeptidase (GGT), Alk Phos ≤ 3 times Unit Line Number (ULN), bilirubin ≤ 40 μmol/L
   * Lactate Dehydrogenase (LDH) ≤ 1,5 times ULN
   * Albumin ≥ 28 g/dL
   * Creatinine clearance ≥ 45 mL/min according to the Modification of the Diet in Renal Disease formula (MDRD)
   * Proteinuria ≤ 1g/dL in the absence of tract infection
10. Cardiac Function satisfactory: Left Ventricular Ejection Fraction (LVEF) determined by myocardial scintigraphy or echocardiography
11. Females of childbearing potential must take acceptable methods of birth control during the complete duration of treatment and serum pregnancy tests must be negative at the inclusion. Men must agree to use a condom if his partner is of child bearing potential
12. Patient receiving a social security system
13. Signed inform consent

Exclusion Criteria:

1. Pregnant or lactating women or childbearing potential refusing methods of birth control
2. Transudative pleural effusion: pleural protein \< 30 g/L and/or Light's criteria when pleural protein is not indicative. Light's criteria are as follows (for diagnosis of transudative):

   * Pleural protein/serum protein ratio \< 0.5
   * Pleural LDH/serum LDH ratio \< 0.6
   * Pleural LDH \< two-thirds the upper limit of normal of serum LDH
3. Purulent pleural effusion.
4. Macroscopically haemorrhagic pleural effusion.
5. Bilateral metastasis pleurisy requiring punctures on both sides.
6. Any co morbidity considered to be incompatible with participation in the study, according to the investigator, particularly: untreated infectious disease, chronic respiratory insufficiency, chronic renal insufficiency, Child Pugh B or C, hepatocellular insufficiency; chronic heart failure not controlled by appropriate medical treatment.
7. Contraindications to intrapleural administration of bevacizumab:

   * Non-controlled arterial or venous thromboembolism
   * Major surgery during the previous month or planned after study
   * Known, non treated brain metastases
   * Known hypersensitivity to bevacizumab or one of its excipients
   * Hypersensitivity to Chinese hamster ovary cell (CHO) products or other human recombinant or humanized antibodies
   * Intravenous administration of bevacizumab planned or underway in the usual cancer treatment (≥ 3 weeks wash out from the intrapleural injection)
   * Radiotherapy including lung field concerned since the administration of the product until the end of the study.
8. Diagnosis of any second malignancy within the last 5 years, except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast) unless the subject has been free of the disease for \> 3 years.
9. Patients can't participate in another clinical trial with another experimental anti-cancer drug therapy simultaneously for 90 days. No exclusion period is required after the end of the trial visit.
10. Impossibility to follow the calendar of exams because of geographic, social or psychological reasons.