A Single-Center, Phase II Clinical Study of HIFU With or Without PD-1 Inhibitors Followed by Abraxane Plus Carboplatin Neoadjuvant Therapy in Triple-Negative Breast Cancer.
Background: Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer with limited treatment options. Research suggests that using High-Intensity Focused Ultrasound (HIFU) to destroy the tumor and/or PD-1 inhibitor drugs to activate the immune system before starting chemotherapy may improve treatment effectiveness. This study aims to investigate this new approach.
Objective: To evaluate the effectiveness and safety of using HIFU, with or without a PD-1 inhibitor (Sintilimab), before and during combination chemotherapy in patients with early-stage TNBC. The primary goal is to determine if this strategy can increase the rate of pathological complete response (pCR). Study
Design: This is a single-center, Phase II clinical study. Approximately 40 participants with Stage II-III TNBC will be enrolled and assigned to one of two groups (cohorts) without randomization: Cohort A: Receives HIFU treatment. Two weeks later, begins standard chemotherapy (Abraxane and carboplatin) combined with the PD-1 inhibitor Sintilimab for 6 cycles. Cohort B: Receives HIFU treatment combined with a single dose of the PD-1 inhibitor Sintilimab. Two weeks later, begins the same 6 cycles of chemotherapy (Abraxane and carboplatin) combined with Sintilimab. Main Measures: The primary measure is the rate of pathological complete response (pCR), defined as the absence of invasive cancer in the breast and lymph nodes after surgery following the completion of neoadjuvant therapy. Other important measures include: The ability of the treatment to activate the immune system (measured by changes in CD8+ T cells or IFN-γ). The percentage of patients whose tumors shrink significantly (Objective Response Rate). How long patients live without their cancer getting worse (Event-Free Survival). The rate of patients who can undergo breast-conserving surgery. The frequency and severity of side effects.
• Female patients aged ≥18 and ≤65 years.
• Histologically confirmed invasive breast cancer, classified as Stage II-III triple-negative breast cancer (TNBC) according to the 8th edition AJCC TNM staging.
• At least one measurable lesion as per RECIST v1.1 criteria.
• No prior chemotherapy, immunotherapy, endocrine therapy, radical surgery, or radiotherapy for breast cancer.
• ECOG performance status of 0 or 1.
• Adequate organ function, defined as:
‣ Hemoglobin ≥90 g/L
⁃ White blood cell count ≥3.5×10\^9/L
⁃ Platelet count ≥100×10\^9/L
⁃ Absolute neutrophil count ≥1.5×10\^9/L
⁃ AST and ALT ≤3× upper limit of normal (ULN)
⁃ Total bilirubin ≤1.5× ULN
⁃ Serum creatinine ≤1.5× ULN
⁃ No evidence of pneumonia on chest CT
• Adequate cardiac function, defined as:
‣ No myocardial ischemia on ECG
⁃ NYHA class I
⁃ LVEF ≥55% on echocardiogram
⁃ Normal cardiac markers (cTnI and BNP)
• Normal thyroid function (T3, T4, FT3, FT4, TSH).
• Willing and able to provide written informed consent.