Neoadjuvant SNF Precision Therapy Phase III

Eligibility Criteria:

• Female patients aged 18 to 70 years.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Histologically confirmed HR-positive/HER2-negative breast cancer (defined as: (1) ER-positive: ≥10% tumor cells positive by immunohistochemistry (IHC).

(2) PR-positive: ≥10% tumor cells positive by IHC. (3) HR-positive: ER and/or PR positive. (4) HER2-negative: HER2 0-1+ by IHC or HER2 2+ with negative FISH (no amplification).

• Confirmed SNF2/3/4 subtype based on H&E staining combined with digital pathology molecular subtyping.

• Clinical tumor stage: cT1c-T2, cN1-N2 or cT3-T4, cN0-N2. 6. Agreement to undergo breast cancer surgery if meeting the criteria for resection after neoadjuvant therapy.

• Adequate organ function, meeting the following criteria: Hemoglobin (Hb) ≥90 g/L; Absolute neutrophil count (ANC) ≥1.5×10⁹/L; Platelet count (PLT) ≥75×10⁹/L; Total bilirubin (TBIL) ≤1.5×ULN (upper limit of normal); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3×ULN; Serum creatinine (Cr) ≤1×ULN; Creatinine clearance rate (CrCl) >50 mL/min (calculated by Cockcroft-Gault formula).

• Baseline left ventricular ejection fraction (LVEF) ≥55% measured by echocardiography or MUGA scan.

• Negative serum pregnancy test for women of childbearing potential. Contraception requirement: Women of childbearing potential must use medically approved contraception during treatment and for at least 3 months after the last dose of the study drug.

10Voluntary participation with signed informed consent, good compliance, and willingness to follow up.

Exclusion criteria

• Stage IV (metastatic) breast cancer.
• History of invasive breast cancer.
• History of ductal carcinoma in situ (DCIS) or lobular carcinoma in situ (LCIS).
• Prior systemic therapy for breast cancer (chemotherapy, endocrine therapy, or anti-HER2 therapy), or prior excisional biopsy/radiotherapy of primary breast tumor and/or axillary lymph nodes (excluding diagnostic biopsy for primary breast cancer or surgery for benign breast tumors).
• Other malignancies within the past 5 years (except cured cervical carcinoma in situ or non-melanoma skin cancer).
• Participation in any other investigational drug study within 4 weeks prior to randomization.
• Peripheral neuropathy ≥ Grade 2 (per NCI-CTCAE v5.0).
• Severe cardiovascular or cerebrovascular diseases within 6 months prior to randomization, including but not limited to:

• Congestive heart failure,
• Unstable angina,
• Severe uncontrolled arrhythmias,
• Clinically significant valvular disease,
• Uncontrolled severe hypertension,
• Myocardial infarction, or
• Cerebrovascular accident.
• Any severe uncontrolled systemic disease that may interfere with the treatment plan, including significant cardiovascular, pulmonary, or metabolic disorders.
• Major surgery within 4 weeks prior to randomization without full recovery, or anticipated need for major surgery during the study treatment.
• Systemic corticosteroid use (>10 mg prednisone equivalent daily) or other immunosuppressants within 2 weeks prior to the first dose of study drug (except for prophylactic anti-allergy or antiemetic purposes).

• Inhaled/topical steroids or physiologic steroid replacement doses (≤10 mg/day prednisone equivalent) are permitted in the absence of active autoimmune disease.
• Administration of anti-cancer vaccines or live vaccines within 4 weeks prior to the first dose of study drug.
• Active autoimmune disease or history of autoimmune disorders (e.g., interstitial lung disease, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyper/hypothyroidism), EXCEPT:

• Vitiligo,
• Childhood asthma/allergies resolved without intervention in adulthood,
• Stable hypothyroidism on hormone replacement,
• Type 1 diabetes on stable insulin therapy.
• Exclusion: Asthma requiring bronchodilators.
• Immunodeficiency (e.g., HIV-positive, congenital/acquired immune deficiency) or history of organ/allogeneic bone marrow transplantation.
• History of interstitial lung disease (except radiation pneumonitis without steroid treatment) or non-infectious pneumonitis.
• Active liver disease, including:

• Hepatitis B (HBsAg-positive with HBV-DNA ≥1000 IU/mL),
• Hepatitis C (HCV-Ab-positive with detectable HCV-RNA), or
• Autoimmune hepatitis.
• Pregnancy or lactation.
• Known hypersensitivity to the study drug(s), its excipients, or severe allergic reactions to monoclonal antibodies.
• History of substance abuse, alcoholism, or drug addiction.
• Uncontrolled psychiatric/neurological disorders (e.g., epilepsy, dementia) or poor compliance.
• Any other condition that may increase study risk, interfere with treatment/outcomes, or render the patient unsuitable for participation per investigator's judgment.