CDK4/6 Inhibitor Intensification and Chemotherapy De-Escalation for Early-stage Luminal-HER2 Breast Cancer

Inclusion Criteria:

1. Female patients aged between 18 and 75 years;
2. Unilateral invasive carcinoma confirmed by histopathological examination;
3. Postoperative pathological stage I early breast cancer: histologically confirmed invasive carcinoma with a maximum tumor diameter not exceeding 2 cm and no lymph node metastasis (N0);
4. Estrogen receptor (ER) expression ≥ 50%;
5. Immunohistochemical and molecular pathology must meet one of the following criteria: HER-2 overexpression (3+) or HER-2 (0-2+) with gene amplification confirmed by fluorescence in situ hybridization (FISH);
6. Histological grade 1-2 or selected grade 3 tumors with at least one of the following additional features: PAM50 or HER2-based subtyping indicating luminal phenotype , or tumor size ≤ 1 cm );
7. Adequate major organ function, defined as:

(1) Hematologic parameters: hemoglobin (HB) ≥ 90 g/L (without blood transfusion within 14 days), absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L, platelet count (PLT) ≥ 100 × 10⁹/L; (2) Biochemical parameters: total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × ULN, serum creatinine (Cr) ≤ 1 × ULN, and calculated creatinine clearance \> 50 mL/min using the Cockcroft-Gault formula; 8) Cardiac function preserved with left ventricular ejection fraction (LVEF) \> 50%; 9) Willing to participate in the study, with signed informed consent, good compliance, and willingness to comply with follow-up requirements.

Exclusion Criteria:

1. Tumors with a maximum diameter exceeding 2 cm and/or presence of positive axillary lymph nodes;
2. HER2-negative status defined as HER2- or HER2+ by immunohistochemistry; or HER2 2+ by immunohistochemistry without gene amplification confirmed by fluorescence in situ hybridization (FISH);
3. Patients who have previously received neoadjuvant therapy or any form of systemic or non-surgical local treatment prior to enrollment, including chemotherapy, targeted therapy, radiotherapy, or endocrine therapy;
4. History of other malignant tumors, excluding cured basal cell carcinoma of the skin and cervical carcinoma in situ;
5. Has metastatic (Stage 4) breast cancer;
6. Pregnant or lactating women, as well as women of childbearing potential who are unable to use effective contraception;
7. Patients currently enrolled in other clinical trials;
8. Severe organ dysfunction involving the cardiovascular, pulmonary, hepatic, or renal systems, including left ventricular ejection fraction (LVEF) \< 50% as assessed by echocardiography; history of severe cardiovascular or cerebrovascular events within 6 months prior to enrollment (e.g., unstable angina, chronic heart failure, uncontrolled hypertension \> 150/90 mmHg, myocardial infarction, or stroke); patients with poorly controlled diabetes mellitus; patients with severe or uncontrolled hypertension;
9. Active severe or uncontrolled infections;
10. Patients with a history of substance abuse involving psychotropic drugs with ongoing dependency, or a documented history of psychiatric disorders that may interfere with study compliance;
11. Patients deemed unsuitable for participation by the principal investigator or designated study physician.