Optimization of Dynamic Neoadjuvant Therapy Strategies for HER2-Positive Breast Cancer Based on HER2-PET/CT Molecular Imaging

A Prospective, Double-Arm Study on the Optimization of Dynamic Neoadjuvant Therapy Strategies for HER2-Positive Breast Cancer Based on HER2-PET/CT Molecular Imaging

This study evaluates HER2-PET/CT-guided dynamic optimization of neoadjuvant therapy in patients with early-stage HER2-positive breast cancer. Based on metabolic response after two cycles, patients receive either intenstified treatment (Arm A) or de-escalation treatment (Arm B), alongside with a concurrent standard-treatment control group (Arm C). The study aims to establish a response-adaptive, imaging-guided treatment paradigm to optimize neoadjuvant therapy in HER2-positive breast cancer.

This is a prospective, two-arm, interventional study. Eligible patients with early-stage HER2-positive breast cancer are enrolled into Arm A (TCbHP: trastuzumab, pertuzumab, docetaxel/nab-paclitaxel, and carboplatin) or Arm B (trastuzumab, pertuzumab, CDK4/6 inhibitor, and aromatase inhibitor), based on molecular subtype and patient preference. Patients in the control group (ArmC) will receive standard TCbHP therapy without intervention. All patients will undergo HER2-PET/CT imaging at baseline and after two cycles of treatment. Metabolic response, defined as a ≥40% reduction in SUVmax of target lesions, guides subsequent therapy: responders continue the initial regimen, while non-responders switch to an alternative strategy (ADC in Arm A or TCbHP in Arm B). The primary endpoint is the total pathological complete response (tpCR) rate in Arm A and ArmB.

Inclusion Criteria:

• Voluntary participation with written informed consent obtained prior to any study-related procedures
• Age ≥ 18 years, male or female.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1
• Histologically confirmed HER2-positive (IHC 3+, or IHC 2+ with ISH amplification) stage I-III (cT1-3/cN0-2) breast cancer
• Tumor diameter ≥ 1.5 cm assessed by imaging, with at least one PET-evaluable lesion present
• Patient must have known estrogen receptor (ER) and progesterone receptor (PR) status. For Arm B, ER expression ≥ 10% and must be strongly positive.
• Adequate bone marrow, liver, and renal function: WBC > 3.0 × 10⁹/L, ANC ≥ 1.5 × 10⁹/L, PLT ≥ 100 × 10⁹/L, Hb ≥ 10.0 g/dL; total bilirubin ≤ ULN (excluding Gilbert's syndrome), ALP ≤ 2.5 × ULN, AST/ALT ≤ 1.5 × ULN; creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 50 mL/min.
• Patients who participate in the trial have good compliance and are willing to comply with the follow-up visit.

Exclusion Criteria:

• Prior treatment with any chemotherapy, anti-HER2 therapy, radiotherapy, or endocrine therapy, etc
• Locally advanced (cT4/cN3) or bilateral breast cancer
• Patients with known allergies to any active ingredients or excipients of investigational medicinal product
• Other malignancy diagnosed within 5 years prior to enrollment, excluding cervical carcinoma in situ and cured melanoma skin cancer
• Left ventricular ejection fraction (LVEF) < 55%
• Uncontrolled hypertension (systolic > 150 mm Hg and/or diastolic > 100 mm Hg)
• Severely cardiovascular disease
• Current known infection with HIV, hepatitis B virus, or hepatitis C virus
• Patients with pulmonary disease requiring continuous oxygen therapy, previous history of bleeding diathesis or patient is currently receiving anti-coagulant therapy, or immunosuppressive agent
• Major surgical procedure or significant traumatic injury
• Patient has other concurrent severe and/or uncontrolled medical conditions.
• Concurrent participation in other interventional clinical trial
• History of receiving any investigational treatment within 28 days prior to randomization
• Pregnant or breast-feeding women or patients not willing to apply highly effective contraception as defined in the protocol
• Inability to lie flat or presence of psychiatric disorders such as claustrophobia