Pyrotinib Maleate, CDK4/6 Inhibitor and Letrozole in Combination for Stage II-III TPBC: a Phase II Trial

Inclusion Criteria

• •(1)Women aged \> 18 years and ≤ 80 years meeting one of the following conditions;
• •1. Those previously receiving ovariectomy, or aged ≥ 60 years
• •2. Those aged \< 60 years who have had 12 consecutive months of amenorrhoea without any pathological or physical causes, and have postmenopausal E2 and follicle stimulating hormone (FSH) levels
• •3. Premenopausal or perimenopausal women who are willing to receive LHRH agonist treatment during the study period
• •(2) Women who have breast cancer histopathologically confirmed by positive estrogen receptor (ER; ≥ 10%), positive progesterone receptor (PR; ≥ 1%), and positive human epidermal growth factor receptor 2 (HER2) according to the 2018 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) human epidermal growth factor receptor 2 (HER2) guideline. ER, PR and HER2 will be assessed by immunohistochemistry (IHC) on harvested tissue. ER, PR and HER2 will be considered positive if the IHC result is positive (score 3+), or the IHC result is positive (2+) and in situ hybridization (ISH) amplification rate (≥ 2.0);
• •(3) Women having stage II-III breast cancer diagnosed based on AJCC cancer staging system (8th edition) who will be admitted because of breast cancer for the first time;
• •(4) Karnofsky Performance Status (KPS) Scale score ≥ 70;
• •(5) The functional level of organs must meet the following requirements:
• •a) Bone marrow function i) Absolute neutrophil count ≥ 1.5 × 109/L (no use of growth factor within 14 days) ii) Platelet count ≥ 100 × 109/L (no corrective treatment within 7 days) iii) Hemoglobin level ≥ 100 g/L (no corrective treatment within 7 days) b) Liver and kidney function i) Total bilirubin ≤1 upper limit of normal value (ULN) ii) Alanine transaminase (ALT) and aspartate transaminase (AST) ≤ 3 × ULN (ALT and AST ≤ 5 × ULN in patients with liver metastasis) iii) Blood urea nitrogen (BUN) and creatinine ≤ 1.5 × ULN and creatinine clearance ≥ 50 mL/min (Cockcroft-Gault formula); c) Color Doppler echocardiography: Left ventricular ejection fraction ≥ 50% d) 12-lead electrocardiography: QTc interval ≤ 480 ms
• •(6) Women who can undergo a biopsy;
• •(7) Volunteers to participate in the study, provision of signed informed consent, good compliance and willingness to cooperate with follow-ups