Intrathecal Chemotherapy Through Ommaya Reservoir Upon Her-2 Negative Breast Cancer With Leptomeningeal Metastasis

Inclusion Criteria: 1. Male or female aged 18 years or above; 2. Can understand the purpose of clinical trials and the benefits and risks, voluntarily participate in and sign the informed consent 3. The physical status score of the Eastern Oncology Consortium (ECOG) was ≤3; 4. HER2-metastatic breast cancer confirmed histologically or cytologically (HER2- is defined as either a standard immunohistochemical (IHC) test result of 0 or 1+, or an IHC test result of 2+ and a negative ISH test result); 5. Failure of standard treatment, or intolerance to standard treatment; 6. pial metastasis is present, which is defined as meningeal metastasis confirmed by malignant tumor cells found in cerebrospinal fluid cytology; Or clinical symptoms/signs suggest meningeal metastasis, and brain MRI suggests pia enhancement; 7. The function of major organs was good, which was confirmed by the following laboratory tests during the screening period: Platelet count ≥80\*10\^9/L Hemoglobin ≥8g/L Neutrophil count ≥1.5\*10\^9/L Serum creatinine ≤1.5\*ULN ALT and AST≤ 3\*ULN (if liver metastases are present, ALT and AST≤5\*ULN) Serum total bilirubin ≤1.5\*ULN International Standardized ratio (INR) and Activated partial thromboplastin time (APTT) ≤1.5\*ULN 8. NYHA cardiac function grade ≤II, no obvious abnormality in ECG, or no clinical significance according to the investigators; 9. Voluntary compliance with the trial protocol during the study period and regular follow-up; 10. For all women of childbearing age, fertile men or their spouses who did not plan to have children or donate sperm during the entire trial period until 6 months after the last dose, or who voluntarily took effective contraception, the blood/urine pregnancy test results of female patients of childbearing age within 7 days before enrollment were negative. 11. Subjects who have recovered from non-hematological toxicity from the last treatment (CTCAE≤ class 1, except for special conditions such as "alopecia") before first administration, and who the investigator determines that the corresponding AE does not pose a safety risk. Exclusion Criteria: 1. Pregnant or lactating women; 2. Patients with acute and chronic infections, or with other serious diseases at the same time, were judged not suitable for this study; 3. Other malignant tumors within 5 years (except the following cases: cured skin basal cell carcinoma, cervical carcinoma in situ, thyroid papillary carcinoma; A second primary cancer that has been eradicated and has not recurred within five years; Both primary cancers are expected to benefit from this study. Investigators have identified the primary tumor source of the metastases); 4. Mental illness or mental disorder, poor compliance can not cooperate with and describe treatment response; 5. There are serious organic diseases or major organ failure, such as decompensated heart and lung failure, which can not tolerate treatment; 6. Patients with bleeding tendency; 7. Patients who have received organ transplants; 8. Patients taking adrenal corticosteroids or immunosuppressants for a long time; 9. Intracranial hemorrhage unrelated to tumor disease; 10. Patients with central nervous system complications requiring urgent treatment; 11. Test group: subjects who could not collect CSF; 12. The subject has a history of immunodeficiency, including HIV testing positive, or other acquired or congenital immunodeficiency diseases; 13. Active viral hepatitis B (HBsAg positive with HBV DNA≥500 IU/mL) or hepatitis C. Among hepatitis C antibody positive subjects, only those whose polymerase chain reaction showed negative HCV RNA were eligible for enrollment (chronic hepatitis B or chronic hepatitis C patients with stable disease receiving standard antiviral therapy were eligible for enrollment); 14. The subject has a serious cardiovascular clinical disease or symptom, including: Congestive heart failure History of unstable angina; myocardial infarction within the past six months; Clinically significant malignant arrhythmias (except atrial fibrillation and paroxysmal supraventricular tachycardia); Subjects had clinically significant prolonged QTcF High blood pressure that is not well controlled; 15. The researcher believes that the patient has other conditions that are not suitable for participating in this study.