Neoadjuvant With Trastuzumab, Pyrotinib Plus Palbociclib and Fulvestrant in HER2-positive, ER-positive Breast Cancer

Inclusion Criteria: 1. Age: 18 or older than 18; 2. Postmenopausal; Pre-menopausal and peri-menopausal female patients must receive ovarian function inhibitors or ovariectomy concurrently. 3. Have not received chemotherapy or endocrine therapy in the past; 4. Have been confirmed as breast invasive ductal carcinoma by the imaging examination and pathological biopsy; 5. Patients with locally advanced breast cancer, stage IIa-IIIa 6. HER2 status to be centrally confirmed (HER2 3+ of neu amplified) 7. Positive estrogen receptor (ER) \> 10% 8. Estimated survival \> 12 months; 9. ECOG physical status score before treatment is 0-1 points; 10. The patient has a measurable lesion (according to the standard RECIST 1.1); 11. Willing to cooperate with pre-treatment needle biopsy and neoadjuvant therapy; 12. No serious metastasis, no brain metastasis, no liver metastasis; 13. Normal bone marrow function, blood neutrophils ≥ 1.5x109 / L, hemoglobin ≥ 100g / L, platelets ≥ 100x109 / L; 14. normal liver and kidney function, blood AST≤60U/L, total bilirubin ≤2.5 times of the normal upper limit, and serum creatinine ≤110µmol/L, urea nitrogen ≤7.1mmol/L; 15. No abnormal blood coagulation; 16. Normal heart function, normal ECG and LVEF ≥ 55%; 17. Women of childbearing age are willing to take reliable contraceptive measures during clinical trials, and the serum or urine pregnancy test is negative within 7 days before administration; no coagulation abnormality; 18. Sign the informed consent form (ICF) and voluntarily receive follow-up visits, treatment, laboratory tests and other study procedures as planned. \- Exclusion Criteria: 1. Have performed any local or systemic treatment (including chemotherapy, radiotherapy, targeted drug therapy, experimental treatment, etc.) for the breast cancer; 2. Inflammatory breast cancer, bilateral breast cancer or breast cancer with distant metastasis found; 3. Subjects with uncontrolled lung disease, severe infection, active gastrointestinal ulcer, coagulopathy, severe uncontrolled diabetes, connective tissue disease or inhibition of bone marrow function who cannot tolerate neoadjuvant therapy and related therapy; 4. Peripheral neuropathy caused by any factor \> 1 degree; 5. Subjects who previously have a history of congestive heart failure, uncontrolled or symptomatic angina, arrhythmia or myocardial infarction, and uncontrollable hypertension (systolic blood pressure \> 180 mmHg or diastolic blood pressure \> 100 mmHg); 6. Previous extensive radiotherapy 7. Current use or anticipated need for food or drugs that are known strong CYP3A4 (cytochrome P450 3A4) inhibitors or inducers. 1. Strong CYP3A inhibitors, including, boceprevir, clarithromycin, conivaptan, delavirdine, indinavir, itraconazole, ketoconazole, lopinavir, mibefradil, miconazole, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, suboxone, telaprevir, telithromycin, voriconazole, and grapefruit, grapefruit juice or any product containing grapefruit. 2. Strong CYP3A inducers, including carbamazepine, phenytoin, primidone, rifampin, rifapentin, and St. John's wort. 8. Breast cancer during the lactation period and gestation period; 9. Reluctance to receive pre-treatment biopsy and neoadjuvant therapy; 10. Psychiatric patients or other factors that cause non-compliance with the treatment; 11. Subjects who are known to have a history of severe allergies to any drug in the treatment regimen; patients who have undergone major surgery or severe trauma within 2 months prior to the first administration; subjects who currently or recently (within 30 days prior to enrolment) have used another investigational drug or participated in another study; 12. Subjects who are known to have infected with human immunodeficiency virus (HIV); 13. Subjects who have other conditions unsuitable for inclusion as considered by investigators, combined with CYP3A4 inhibitors or inducers; 14. Subjects with long QT syndrome or QTc \> 470 ms. 15. According to the judgement of the researchers, there are concomitant diseases that seriously endanger the safety of patients or affect the completion of research (including, but not limited to, severe hypertension, severe diabetes, active infections, etc.). 16. Moderate infection occurs within 4 weeks before the first administration (e.g. intravenous drip of antibiotics, antifungal or antiviral drugs according to clinical criteria), fever of unknown origin occurs during the screening period/before the first administration. \-