Pilot Study of Neoadjuvant Chemotherapy Combined With Immunotherapy and Multimodal Thermal Therapy for HER2-negative Breast Cancer

Local tumor destruction with non-surgical ablation (NSA, cryoablation or radiofrequency) induces inflammation and releases antigens that can activate tumor-specific immune responses.

Pre-clinically, we demonstrated that multimodal thermal therapy (MTT) as an integrated treatment modality of cryotherapy and radiofrequency heating, can effectively activate systemic and long-lasting antitumor immunity.

In this pilot study, patients with operable HER2-negative breast cancer were designed to receive a combination of MTT, immunotherapy and neoadjuvant chemotherapy. Potential favorable intra-tumoral and systemic immunologic effects were assessed with the combination, revealing the possibility for induced and synergistic anti-tumor immunity with this strategy.

Inclusion criteria

• Female，age 18-70 years.
• Histologically confirmed invasive cancer of the breast, and patients meeting cT2-4N+M0 criteria;
• TNBC non-immunoregulation subtype or HR+/HER2- status were measured by immunohistochemistry (IHC);
• At least one measurable lesion according to RECIST 1.1 criteria;
• Normal organ and marrow function: Hemoglobin (HB) ≥90 g/L (No blood was transfused within 14 days), Absolute neutrophil count ≥ 1500/μL, Platelets ≥ 75,000/μL, Total bilirubin ≤ 1.5 x ULN), aspartate aminotransferase (AST) (SGOT) and alanine aminotransferase (ALT) (SGPT) ≤ 3 x ULN, creatinine < 1 x ULN, endogenous creatinine clearance > 50 ml/min (Cockcroft-Gault formula);
• LVEF ≥55%;
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1;
• Non-pregnant and non-lactating, fertile female subjects were required to use a medically approved contraceptive method for the duration of the study treatment and at least 3 months after the last use of the study drug;
• Ability to understand and willingness to sign a written informed consent.

Exclusion criteria

• Previous cytotoxic chemotherapy, endocrine therapy, biological therapy or radiotherapy for any reason;
• Patients with New York Heart Association (NYHA) grade II or above heart disease (including grade II);
• Patients with severe systemic infections or other serious diseases;
• Patients with known allergy or intolerance to the study drug or its excipients;
• Other malignant tumors in the past 5 years, except cured cervical carcinoma in situ and non-melanoma skin cancer;
• Pregnant or lactating patients of childbearing age who refused to take appropriate contraceptive measures during the course of the study;
• Participated in other trial studies within 30 days before the administration of the first dose of the study drug;
• Endocrine system disorders;
• Patients who were judged by the investigator to be unsuitable for this study.