Clinical Study of Fulvestrant Combined With Chidamide in the Treatment of Hormone Receptor-positive Advanced Breast Cancer Resistant to CDK4/6 Inhibitors

Inclusion Criteria:

• age ≥ 18 years, postmenopausal * female patients;
• histologically or cytologically confirmed hormone receptor positive (ER positive, PR positive or negative), human epidermal growth factor receptor 2 negative # breast cancer patients;
• the disease before enrollment is overall unresectable locally advanced or metastatic breast cancer, and at least one measurable lesion or no measurable lesion and bone metastasis alone patients;
• for locally advanced or metastatic breast cancer, previous progression by first-line aromatase inhibitors combined with Cyclin-dependent kinases（CDK）4/6 inhibitors;
• the total number of regimens regardless of rescue therapy or adjuvant therapy before enrollment is ≤ 3, of which the number of rescue chemotherapy regimens is ≤ 1;
• Eastern Collaborative Oncology Group（ECOG） score 0-1;
• absolute neutrophil count ≥ 1.5 × 109/L, platelets ≥ 100 × 109/L, hemoglobin ≥ 90 g/L;
• expected survival time ≥ 3 months;
• Voluntarily participate in this clinical trial and sign the written informed consent form

Exclusion Criteria:

• no measurable lesions (except simple bone metastasis), such as pleural or pericardial exudate, ascites, etc.;
• underwent major surgical procedures or significant trauma before enrollment, or patients are expected to undergo major surgical treatment;
• Patients who have previously been treated with fulvestrant or histone deacetylase inhibitors (including romidepsin, vorinostat), but have received only one cycle (≤ 2 times, d1, d15, respectively) of fulvestrant within 28 days (before enrollment) are allowed;
• known to have a history of allergy to the drug components of this protocol;
• the presence of brain (membrane) metastasis during the screening period;
• a history of immunodeficiency, including HIV test positive, or suffering from other acquired, congenital immunodeficiency diseases, or a history of organ transplantation;
• uncontrolled important cardiovascular disease;
• abnormal liver function [total bilirubin > 1.5 times the upper limit of normal; alanine aminotrans（ALT）/aspartate aminotransferase（AST） > 2.5 times the upper limit of normal in patients without liver metastasis, alanine aminotrans（ALT）/aspartate aminotransferase（AST） > 5 times the upper limit of normal in patients with liver metastasis], abnormal renal function (serum creatinine > 1.5 times the upper limit of normal);
• pregnant, lactating female patients or women of childbearing potential baseline pregnancy test positive; or during the study and the last dose of at least 8 to take effective contraceptive measures in subjects of childbearing age;
• According to the investigator's judgment, there are concomitant diseases that seriously endanger the patient's safety or affect the patient's completion of the study (such as: severe hypertension, diabetes, thyroid disease, active infection, etc.);
• History of definite neurological or psychiatric disorders, including epilepsy or dementia;
• Unsuitable for participation in the study as judged by the investigator.