Efficacy and Safety of Trastuzumab Rezetecan Followed by CDK4/6 Inhibitors and Endocrine Therapy in HR+/HER2-Low/Ultra-Low Advanced Breast Cancer

Inclusion Criteria: Participants must meet all of the following criteria: 1\. Female patients aged ≥18 years. 2. Pathologically confirmed HER2-low/ultra-low, HR-positive unresectable or metastatic breast cancer: 1. HER2-low: IHC 1+ or IHC 2+/ISH-negative；HER2-ultra-low: IHC 0 with membranous staining (\>0 but \<1+). HR+: ≥10% tumor cells with ER/PR nuclear staining (verified by central pathology review). 2. Disease stage: Recurrent/metastatic disease; locally recurrent cases must be deemed unresectable by investigators. 3\. Prior therapy: 1. Disease progression after endocrine therapy (ET) + CDK4/6 inhibitor in the advanced/metastatic setting. 2. Progression within 12 months of adjuvant ET + CDK4/6 inhibitor allowed. 3. ≤1 line of prior ET and ≤1 line of chemotherapy for advanced disease. 4. Measurable disease per RECIST 1.1 (including lytic/mixed bone-only metastases). 5\. ECOG PS 0-1. 6. Adequate organ function (no transfusions/G-CSF within 2 weeks prior): 1. Hematologic: ANC \>1.5×10⁹/L; platelets \>90×10⁹/L; Hb \>90 g/L. 2. Hepatic: Total bilirubin ≤ULN (≤2×ULN if Gilbert's syndrome). ALT/AST ≤1.5×ULN (≤5×ULN with liver metastases). Alkaline phosphatase ≤2.5×ULN. 3. Renal: BUN/Cr ≤1.5×ULN. 4. Cardiac: LVEF ≥50%; 5. QTcF \<470 ms. 7. Voluntary participation with signed informed consent. Exclusion Criteria: Participants will be excluded if they meet any of the following conditions: 1. Prior anti-HER2 therapy at any stage (including HER2-ADCs such as T-DM1 or T-DXd). 2. Significant cardiac disease, including: 1\) Heart failure or systolic dysfunction (LVEF \<50%). 2) High-risk/treated angina or arrhythmias (e.g., Type II Mobitz II/third-degree AV block, ventricular tachycardia). 3\) Clinically significant valvular disease. 4) ECG-confirmed transmural myocardial infarction. 5) Uncontrolled hypertension (systolic \>150 mmHg and/or diastolic \>100 mmHg). 3. Interstitial lung disease (ILD)/pneumonitis: 1. History of non-infectious ILD requiring steroids. 2. Current ILD or suspected ILD that cannot be ruled out by imaging at screening. 4. Impaired drug absorption due to: 1\) Dysphagia, chronic diarrhea, intestinal obstruction, or other factors affecting oral medication intake. 5\. Uncontrolled third-space effusions (e.g., pleural/peritoneal effusions) not manageable by drainage. 6\. Pregnancy, lactation, or unwillingness to use effective contraception during and for 7 months post-treatment. 7\. Other exclusions: 1. Severe comorbidities interfering with treatment (e.g., active HBV, pulmonary infections requiring therapy). 2. Any condition deemed unsuitable by investigators.