Inclusion Criteria:
1. Age ≥18 years old;
2. Invasive breast cancer confirmed by histological or cytological examination,
accompanied by metastatic disease; Patients with metastatic diseases not confirmed
by pathology or cytology should obtain clear evidence of metastasis through physical
examination or radiological research;
3. Based on the pathological report of recent biopsy or other pathological specimens
(confirmed by the laboratory of the participating research center), the histology
and/or cytology are confirmed as triple negative breast cancer. The specific
requirements include: a) the definition of negative human epidermal growth factor
receptor 2(HER2): the immunohistochemistry (IHC) is 0 or 1+; If IHC was 2+, it was
confirmed negative by fluorescence in situ hybridization (FISH). B) Negative
estrogen and progesterone receptors means that IHC examination shows ER < 10% and or
PR < 10%, and the researcher evaluates that patients cannot benefit from endocrine
therapy.
4. Newly diagnosed brain metastases or brain metastases that have progressed after
local treatment: patients with brain metastases who met all the criteria of this
scheme before starting from September 1, 2023 and did not meet all the exclusion
criteria can also be included;
5. Patients must have measurable central nervous system diseases, defined as at least
one brain parenchymal lesion, which can be accurately measured in at least one
dimension through local radiological examination; And there is no central nervous
system symptom or symptom controllable, so radiotherapy is not needed urgently.
6. Patients who have previously received at least one taxane and/or one anthracycline
antibiotic (as a treatment history of neoadjuvant therapy, adjuvant therapy or
metastatic therapy or both);
7. Allow (new) adjuvant therapy to have recurrence and metastasis after stopping using
Utterone and/or Capecitabine for more than one year, or stop taking drugs for
non-progressive reasons in the rescue stage;
8. The physical status score (ECOGPS) of the eastern cancer cooperative group is 0-2,
and the life expectancy is more than 12 weeks;
9. Normal organ and bone marrow function; Blood routine examination was basically
normal within one week before joining the group (based on the normal laboratory of
each research center): neutrophil count (ANC) ≥ 1.5× 109/L; Hemoglobin (HB) ≥ 90g/L;
Platelet count (PLT) ≥ 75× 109/L; Liver and kidney function tests were basically
normal within one week before enrollment (based on the normal values of laboratories
in each research center): total bilirubin (TBIL)≤1.5× upper limit of normal value
(ULN); Alanine aminotransferase (SGPT/ALT)≤2.5×ULN (patients with liver metastasis ≤
5 XULN); Aspartate aminotransferase (SGOT/AST)≤2.5× upper limit of normal value
(ULN); Creatinine clearance rate (Ccr)≥60ml/min.
10. Neuropathy should be < grade 2 within 4 weeks before enrollment (version 5.0 of
ncictcae);
11. No major organ dysfunction and no heart disease;
12. Women and male patients with reproductive potential must agree to use appropriate
contraceptive measures before the start of the study and during the study
participation.
Exclusion Criteria:
1. Patients with extensive meningeal metastasis and brain metastasis who are
ineffective in dehydration treatment with hormones or in urgent need of
radiotherapy;
2. Invasive breast cancer confirmed by histological or cytological examination,
accompanied by metastatic disease; Patients with metastatic diseases not confirmed
by pathology or cytology should obtain clear evidence of metastasis through physical
examination or radiological research;
3. Received chemotherapy, major surgery, targeted therapy or immunotherapy within 2
weeks before joining the group (the interval between targeted therapy and
immunotherapy is at least 2 weeks or at least 5 half-lives, whichever is shorter);
Received endocrine therapy within 1 week before joining the group; He had received
nitrosourea or mitomycin chemotherapy within 6 weeks before joining the group;
4. Receive unlisted clinical trial drugs within 4 weeks before entering the group;
5. Previous history of grade 3 or 4 allergic reactions related to Utterone or
Capecitabine;
6. inability to swallow, chronic diarrhea and intestinal obstruction, there are many
factors that affect the taking and absorption of drugs;
7. Known contraindications for gadolinium MRI contrast agents, such as pacemakers,
shrapnel or ocular foreign bodies;
8. Suffering from other malignant tumors in the past 3 years, excluding cured cervical
carcinoma in situ, basal cell carcinoma of skin, squamous cell carcinoma of skin or
early thyroid carcinoma;
9. Seizures occurred more than 2 times within 4 weeks before joining the group;
10. Poor control of hypertension; Or have a history of hypertensive crisis or
hypertensive encephalopathy;
11. Have a history of bleeding in the central nervous system of grade 3 or above within
12 months;
12. Suffering from serious or uncontrollable diseases, including but not limited to: 1)
active virus infection, such as HIV and HBV active phase (HbsAg positive and
HBV-DNA≥103, hepatitis C antibody positive); 2) Suffering from severe cardiovascular
disease in the past: uncontrollable hypertension; Myocardial infarction, unstable
arrhythmia, congestive heart failure, pericarditis, myocarditis, etc. According to
NYHA criteria, patients with grade Ⅲ ~ Ⅳ cardiac insufficiency, or those with left
ventricular ejection fraction (LVEF) less than 50% indicated by echocardiography;
12. Suffering from serious or uncontrollable diseases, including but not limited to:
1) active virus infection, such as HIV and HBV active phase (HbsAg positive and
HBV-DNA≥103, hepatitis C antibody positive); 2) Suffering from severe cardiovascular
disease in the past: uncontrollable hypertension; Myocardial infarction, unstable
arrhythmia, congestive heart failure, pericarditis, myocarditis, etc. According to
NYHA criteria, patients with grade Ⅲ ~ Ⅳ cardiac insufficiency, or those with left
ventricular ejection fraction (LVEF) less than 50% indicated by echocardiography;
13. Have a history of hemoptysis within 6 months before joining the group; Or evidence
of bleeding tendency or obvious coagulation dysfunction in the last month;
14. Currently receiving full-dose warfarin or equivalent drugs, or taking aspirin
(325mg/ day) within 10 days; 15.28 days or in the course of the study, it is
expected that major surgery, open biopsy or major trauma are needed;
16. Those who have a history of abdominal fistula or gastrointestinal perforation in the
first 6 months; There are unhealed wounds, active ulcers or untreated fractures;
Pregnant or lactating women; 17. Those who have a history of psychotropic substance
abuse and cannot quit or patients with mental disorders; 18. According to the
judgment of the researcher, there are other patients with accompanying diseases that
seriously endanger the safety of patients or affect the completion of the study; 19.
Those who are known to have allergic history to the drug components of this scheme;
Have a history of immunodeficiency, including HIV positive, HCV or other acquired or
congenital immunodeficiency diseases, or have a history of organ transplantation;
20. The history of live attenuated vaccine inoculation within 28 days before the
first study or the person who is expected to be vaccinated with live attenuated
vaccine in the study; 21. Any situation that the researcher thinks is not suitable
for this study.
