Toripalimab Combined With Anthracycline-free or Anthracycline-containing Chemotherapy as Neoadjuvant Chemotherapy for Early Triple Negative Breast Cancer

A Prospective, Randomized Controlled, Multicenter Phase II Clinical Study of Toripalimab Combined With PCb-EC Regimen (Albumin Paclitaxel + Carboplatin Followed by Epirubicin + Cyclophosphamide) or PCb Regimen (Albumin Paclitaxel + Carboplatin) as Neoadjuvant Therapy for Triple-Negative Breast Cancer

This study aims to evaluate the efficacy and safety of a PD-1 inhibitor combined with different chemotherapy regimens (PCb-EC and PCb), in order to develop a superior and well-tolerated neoadjuvant therapeutic strategy for patients with triple-negative breast cancer.

Inclusion Criteria:

1. Age: 18-70 years.
2. Disease Status: Clinical pathological confirmation of cT2-cT4d, or cT1c with axillary lymph node metastasis.
3. Pathology: Histopathologically confirmed triple-negative, invasive breast carcinoma.
4. Definition of Triple-Negative Breast Cancer:
5. ER and PR negative (IHC nuclear staining <10%).
6. Her-2 negative (IHC 0 or 1+ without FISH, or IHC 2+ with FISH demonstrating no amplification).
7. Measurable Disease: Presence of clinically measurable lesion(s) confirmed by ultrasound, mammography, or optional MRI within 1 month prior to randomization.
8. Adequate Organ and Bone Marrow Function (within 1 month prior to chemotherapy), indicating no contraindications for chemotherapy:
9. Absolute Neutrophil Count (ANC) ≥ 1.5 × 10⁹/L
10. Hemoglobin (Hb) ≥ 90 g/L
11. Platelet count (PLT) ≥ 100 × 10⁹/L
12. Total Bilirubin (TBIL) < 1.5 × ULN (Upper Limit of Normal)
13. Serum Creatinine (Cr) < 1.5 × ULN
14. Aspartate Aminotransferase (AST) / Alanine Aminotransferase (ALT) < 1.5 × ULN
15. Cardiac Function: Left ventricular ejection fraction (LVEF) ≥ 50% as measured by echocardiogram.
16. Pregnancy Status: For women of childbearing potential, a negative serum pregnancy test within 14 days prior to randomization.
17. Performance Status: Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 1.
18. Informed Consent: Signed informed consent obtained.

Exclusion Criteria:

1. Metastatic Disease: Evidence of metastatic breast cancer. (To exclude metastasis, CT scans of the chest and abdomen, and a bone scan must be performed at any time point from diagnosis to randomization; PET/CT may serve as an alternative imaging modality).
2. Prior Anti-Cancer Therapy: Any prior chemotherapy, endocrine therapy, targeted therapy, or radiotherapy for the current breast cancer.
3. Second Primary Malignancy: Presence of a second primary malignancy, except for:
4. Adequately treated non-melanoma skin carcinoma.
5. Prior Immunotherapy: Previous treatment with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or any other immunomodulatory therapy.
6. Immunodeficiency or Autoimmune Disease: Diagnosed immunodeficiency or active autoimmune disease requiring systemic treatment.
7. Severe Comorbidities: Severe or uncontrolled pulmonary or cardiac disease.
8. Active Hepatitis: Active Hepatitis B or Hepatitis C infection.
9. Transplantation History: History of solid organ or bone marrow transplantation.
10. Pregnancy/Lactation: Pregnant or lactating women.
11. Other Medical Conditions: Any other severe, uncontrolled medical condition that, in the investigator's judgment, constitutes a contraindication to chemotherapy.