Entinostat and Pyrotinib for Advanced Breast Cancer

Inclusion Criteria: 1. Age ≥ 18 and ≤ 75 years, female, premenopausal or postmenopausal. 2. Histologically confirmed HR+/HER2+ breast cancer (HER2 positive defined as IHC 3+ or FISH confirmed by the pathology department of the study center). 3. Histologically confirmed locally advanced breast cancer (not amenable to curative local therapy) or recurrent/metastatic breast cancer. 4. Prior treatment with trastuzumab and taxane-based anticancer therapy. 5. Received 1-2 prior lines of systemic anticancer therapy in the advanced setting. 6. Life expectancy ≥ 3 months. 7. At least one measurable lesion per RECIST v1.1. 8. ECOG performance status 0-2. 9. All acute toxicities from prior anticancer therapy resolved to Grade 0-1 (per NCI CTCAE v5.0), except alopecia and toxicities deemed by the investigator to pose no safety risk. 10. Adequate bone marrow function: ANC ≥ 1.5×10\^9/L, platelet ≥ 100×10\^9/L, hemoglobin ≥ 90 g/L. 11. Adequate hepatic and renal function: TBIL ≤ 1.5×ULN; ALT and AST ≤ 2.5×ULN (or ≤ 5×ULN in the presence of liver metastases); BUN and Cr ≤ 1.5×ULN with creatinine clearance ≥ 50 mL/min. 12. Voluntarily participate and sign written informed consent. - Exclusion Criteria: 1. Factors significantly affecting oral drug absorption, such as inability to swallow, chronic diarrhea, or intestinal obstruction. 2. Prior treatment with any HDAC inhibitor for antitumor therapy. 3. Prior or current use of any HER2-targeted tyrosine kinase inhibitor (including lapatinib, neratinib, pyrotinib, etc.). 4. Known allergy to any component of the study drugs. 5. Other malignancy within 5 years prior to enrollment, except cured papillary thyroid carcinoma, cervical carcinoma in situ, basal cell carcinoma, or squamous cell carcinoma of the skin. 6. Participation in another drug clinical trial within 4 weeks prior to enrollment. 7. History of immunodeficiency, including HIV positivity, other acquired or congenital immunodeficiency diseases, or history of organ transplantation. 8. Uncontrolled significant cardiovascular disease: clinically significant QTc interval prolongation or QTc \> 450 ms at screening; severe cardiac impairment (NYHA \> Class II); unstable angina or myocardial infarction within 6 months; or severe arrhythmia. 9. Pregnant or lactating women, or positive pregnancy test at baseline; or women of childbearing potential who are unwilling to use effective contraception during the study and for at least 8 weeks after the last dose. 10. Concomitant diseases that, in the investigator's judgment, could seriously endanger patient safety or affect study completion (e.g., severe hypertension, diabetes, thyroid disease, active infection). 11. Known history of neurological or psychiatric disorders, including epilepsy or dementia. 12. Active hepatitis (HBV: HBsAg positive with HBV DNA ≥ 500 IU/mL; HCV: HCV antibody positive with HCV RNA \> ULN). 13. Any condition that, in the investigator's judgment, makes the patient unsuitable for study participation. \-