This is an investigator-initiated randomized controlled, open-label, multicenter, prospective Phase 2 clinical study. Patients with stage II-III HR +/HER2 + breast cancer were randomly divided into two groups at a ratio of 1:1. The experimental group received pyrotinib combined with trastuzumab, dalpiciclib and letrozole; the control group received trastuzumab combined with pertuzumab, docetaxel and carboplatin. The main study objective was to evaluate the efficacy and safety of neoadjuvant therapy for HR +/HER2 + breast cancer in the two groups.

Inclusion Criteria:

1. Female patients aged 18 -75 ;
2. Willing to receive LHRH agonist therapy (premenopausal patients only);
3. All patients were histopathologically confirmed to be estrogen receptor (ER) -positive and HER2-positive.
4. Treatment-naïve stage II-III patients with tumor stage meeting AJCC version 8 criteria;
5. ECOG score 0-1;
6. Organ function level must meet the following requirements:

(1) bone marrow function • ANC ≥ 1.5 x 109/L ; • PLT ≥ 100 × 109/L • Hb ≥ 90 g/L ; (2) hepatic and renal function • TBIL ≤ 1.5 × ULN; • AL and AST ≤ 3 × ULN (ALT and AST ≤ 5 × ULN in patients with liver metastases); • BUN and Cr ≤ 1.5 × ULN and creatinine clearance ≥ 50 mL/min; (Cockcroft-Gault formula) (3) Echocardiography: LVEF ≥ 50%; (4) 12-lead ECG: QT interval ≤ 480 ms; 7. Able to undergo needle biopsy; 8. Voluntarily join this study to sign informed consent, have good compliance and willing to cooperate with follow-up.

Exclusion Criteria:

1. Received any form of anti-tumor therapy (chemotherapy, radiotherapy, molecular targeted therapy, endocrine therapy, etc.);
2. Received any other anti-tumor therapy at the same time;
3. Bilateral breast cancer, inflammatory breast cancer or occult breast cancer;
4. Stage IV breast cancer;
5. Breast cancer without histopathological diagnosis;
6. Other malignant tumors in the past 5 years, except cured cutaneous basal cell carcinoma and cervical carcinoma in situ;
7. Severe heart, liver and kidney and other vital organ dysfunction;
8. Inability to swallow, chronic diarrhea and intestinal obstruction, there are a variety of factors affecting drug administration and absorption;
9. Participated in other drug clinical trials within 4 weeks before enrollment;
10. Known history of hypersensitivity to the drug components of this protocol; history of immunodeficiency, including positive HIV test, HCV, active viral hepatitis B or other acquired, congenital immunodeficiency diseases, or history of organ transplantation;
11. Had any cardiac disease, including: (1) cardiac arrhythmia requiring medication or clinically significant; (2) myocardial infarction; (3) heart failure; (4) any other cardiac disease judged by the investigator to be inappropriate for participation in this trial;
12. Female patients who are pregnant or lactating, female patients of childbearing potential with a positive baseline pregnancy test, or female patients of childbearing age who are unwilling to take effective contraceptive measures throughout the trial;
13. According to the investigator 's judgment, there are concomitant diseases that seriously jeopardize the patient' s safety or affect the patient 's completion of the study (including but not limited to uncontrolled severe hypertension, severe diabetes, active infection, etc.);
14. Had a documented history of neurological or psychiatric disorders, including epilepsy or dementia.Any other condition that, in the opinion of the investigator, would make the patient inappropriate for participation in this study.