Neoadjuvant Trastuzumab, Pertuzumab Plus Metronomic Vinorelbine for Elderly HER2-Positive Breast Cancer

Inclusion Criteria:

• Subjects voluntarily participate in this study and sign informed consent.
• Age ≥70 years at the time of informed consent signing.
• ECOG performance status (PS) 0-1; expected survival >3 months.
• Primary HER2-positive breast cancer confirmed by histopathology or cytology.
• Primary tumor diameter >2 cm, or axillary lymph node metastasis.
• Laboratory indicators conform to the following standards:

Absolute neutrophil count (ANC) ≥1.5×10⁹/L; Absolute lymphocyte count (LC) ≥0.5×10⁹/L; Platelet count (PLT) ≥100×10⁹/L; Hemoglobin (Hb) ≥90 g/L; White blood cell count (WBC) 3.0×10⁹/L ≤ WBC ≤15×10⁹/L. Serum biochemistry (no blood transfusion or albumin infusion within 7 days before screening): ALT and AST ≤2.5×ULN; ALT and AST ≤5×ULN in patients with hepatic metastases. ALP ≤2.5×ULN (≤5×ULN for patients with bone tumor metastasis). BUN and Cr ≤1.5×ULN, and creatinine clearance ≥60 mL/min (Cockcroft-Gault formula).

PT and APTT ≤1.5×ULN, INR ≤1.5×ULN (patients not receiving anticoagulation therapy).

Urine protein <2+. If urine protein ≥2+, 24-hour urinary protein quantification ≤1 g.

Thyroid-stimulating hormone (TSH) ≤ULN. Left ventricular ejection fraction (LVEF) ≥50%. Patients with abnormal TSH may be enrolled as long as T3 and T4 levels are normal.

Exclusion Criteria:

• Stage Ⅳ metastatic breast cancer, or patients who cannot undergo curative surgical resection after neoadjuvant therapy as assessed by investigators.
• Prior anti-tumor therapies including chemotherapy, endocrine therapy, anti-HER2 biological therapy, or previous breast surgery (excluding diagnostic biopsy for primary breast cancer).
• Other malignancies diagnosed within 3 years or concurrent malignant tumors at enrollment.
• The following cases are eligible: Other malignancies treated solely by surgery with continuous 5-year disease-free survival (DFS); cured cervical carcinoma in situ, non-melanoma skin cancer, superficial bladder tumors (Ta: non-invasive tumor, Tis: carcinoma in situ, T1: basement membrane-invasive tumor).
• Major surgery, incisional biopsy or severe traumatic injury within 28 days before study treatment (excluding diagnostic biopsy of primary breast cancer).
• Persistent unhealed wounds or fractures.
• History of uncontrolled psychoactive drug abuse or psychiatric disorders.

Severe and/or uncontrolled underlying systemic diseases, including:

1. History of hypertensive crisis or hypertensive encephalopathy; uncontrolled hypertension (systolic blood pressure >150 mmHg or diastolic blood pressure >100 mmHg after antihypertensive treatment).
2. Confirmed heart failure or cardiac systolic dysfunction (LVEF <55%).
3. Grade ≥2 myocardial ischemia, myocardial infarction, arrhythmia (QTc ≥450 ms for males, QTc ≥470 ms for females), or grade ≥2 congestive heart failure (NYHA classification).

4. Angina pectoris requiring anti-anginal medication.

   • Comorbidities interfering with scheduled treatment, including severe pulmonary dysfunction, active pulmonary disease, or uncontrolled severe infection (≥Grade 2 per CTCAE 5.0).
   • Allergy to any investigational drug, active ingredients or pharmaceutical excipients.
   • Subjects with comorbidities that threaten safety or affect study completion, or those unsuitable for enrollment according to investigator judgment.