Chidamide/Everolimus for PIK3CA Wild-type/Mutant HR+/HER2- Advanced Breast Cancer

Inclusion Criteria:

• The age at the time of signing the informed consent form is ≥ 18 years old and ≤ 75years old, for menopausal/premenopausal women (premenopausal women need to receiveovarian function suppression treatment at the same time).
• Breast cancer patients with HR positive (ER expression ≥ 10%, PR positive or negative)and HER2 negative (Immunohistochemical(IHC)0,1+; 2+, Fluorescence in situhybridization(FISH) not expanded) confirmed by histology.
• Histologically confirmed locally advanced breast cancer (no radical local treatment)or recurrent and metastatic breast cancer.
• The patients who had previously progressed after the treatment of first-line orsecond-line cyclin-dependent kinases 4 and 6 inhibitors（CDK4/6 inhibitors）of endocrineand whose chemotherapy was ≤ second-line (relapse during the period of newadjuvant/adjuvant treatment or within 12 months after the end of treatment wasregarded as first-line chemotherapy), the PIK3CA gene mutation detection was performeda. PIK3CA Mutant subjects were enrolled in queue A; b. PIK3CA wild-type subjects wereincluded in queue B.
• At least one measurable primary lesion (according to RECIST v1.1 standard) beforeenrollment.
• The Eastern Oncology Collaborative Group (ECOG) physical fitness score is 0-2.
• The toxic and side effects caused by previous anti-tumor therapy were relieved to 0-1levels before the screening period (judged according to The NCI Common TerminologyCriteria for Adverse Events version5.0 (NCICTCAE5.0); except for toxicity thatresearchers believe does not pose a safety risk to the subjects due to hair loss).
• The functional level of organs must meet the following requirements: 1) Blood routine: Absolute neutrophil count(ANC)≥1.5 × 109/L (growth factor not used within 14 days);Platelet(PLT) ≥100 × 109/L (no corrective treatment used within 7 days); Hb ≥ 100 g/L (without corrective treatment within 7 days); 2) Blood biochemistry: Total bilirubin(TBIL) ≤1.5 × upper limits of normal(ULN); Glutamine aminotransferase(ALT),Glutamictransaminase(AST)≤3 × ULN; Glutamine transpeptidase(GGT) ≤2.5 × ULN; If there is livermetastasis, then ALT and/or AST ≤ 5 × ULN; Glutamine transpeptidase GGT ≤5 × ULN; Urea,Blood urea nitrogen (BUN), creatinine (Cr) ≤1.5 × ULN; 3) Cardiac ultrasound: Leftventricular ejection fraction（LVEF）≥ 50%; 4) 12 lead ECG: QT interval (QTcF) corrected byFridericia method, male<450ms, female.
• Expected survival time ≥ 3 months.
• Voluntarily participate in this clinical trial and sign a written informed consentform.

Exclusion Criteria:

• Those who have received any mammalian target of rapamycin（mTOR） and histonedeacetylase（HDAC） inhibitors at any time in the past.
• Received chemotherapy, Targeted therapy, immunotherapy, interventional therapy orother systematic anti-tumor treatment within 4 weeks before the first administrationof the study drug, or received radiotherapy within 3 weeks Note: Nitroso urea orMitomycin C is within 6 weeks before the first use of the study drug, oralfluorouracil and small molecule targeted drugs are within 2 weeks before the first useof the study drug or within 5 half lives of the drug (whichever is longer),Traditional Chinese medicine with anti-tumor indications should be used within 2 weeksbefore the first use of the study drug.
• Subjects who have undergone major surgical procedures or obvious trauma within 4 weeksprior to enrollment, or are expected to undergo major surgical treatment.
• Subjects with brain or subdural metastasis are excluded. Unless its stability has beenmaintained for at least 4 weeks or Asymptomatic brain metastasis can be included inthe group.
• According to the investigator's judgment, there are concomitant diseases (such assevere hypertension, Thyroid disease, hyperlipidemia, active infection, etc.) thatseriously endanger the patient's safety or affect the patient's completion of thestudy.
• Patients with poor control of diabetes shall be determined by the researcher.
• Clinically obvious gastrointestinal abnormalities that may affect drug intake,transport or absorption (such as inability to swallow, chronic diarrhea, Bowelobstruction, etc.).
• Severe cardiovascular injury (greater than a history of congestive heart failure atNew York Heart Association(NYHA) level II, unstable angina or myocardial infarctionwithin the past 6 months, or severe arrhythmia.
• Subjects have active hepatitis (hepatitis B reference: HBsAg positive and hepatitis Bvirus(HBV) DNA ≥ 500 international unit(IU)/ml; hepatitis C reference: hepatitis Cvirus(HCV) antibody positive and HCV copy number>upper limit of normal value);Subjects who are known to be positive for human immunodeficiency virus (HIV).
• Female patients during pregnancy and lactation, female patients with Fertility andpositive baseline Pregnancy test, or those of childbearing age who are unwilling totake effective contraceptive measures during the whole test period and within 90 daysafter the last administration of the study drug.
• Have a clear history of neurological or mental disorders, including epilepsy ordementia, in the past.
• Any medical condition in which the researcher believes that the subject is notsuitable for entry into the study.