Efficacy and Safety of Shen-Ling-Lian-Xia Granule Combined with Neoadjuvant Chemotherapy in Patients with Triple-Negative Breast Cancer: Protocol for a Randomized, Double-Blind, Multicenter Clinical Trial (Preprint)

BACKGROUND Neoadjuvant chemotherapy (NAC) is a crucial component of systemic treatment for triple-negative breast cancer (TNBC), serving as an effective means to reduce recurrence rates and improve survival outcomes. It not only maximizes the extent of resectable tumors but also converts inoperable tumors into operable ones. Shen-Ling-Lian-Xia Granules (SLLXG) is an in-house preparation developed by Longhua Hospital, affiliated with Shanghai University of Traditional Chinese Medicine. Formulated by Professor Liu Sheng, the fifth-generation inheritor of the Shanghai Gu School of Surgery, based on extensive clinical experience treating breast cancer, this compound has been clinically proven to improve postoperative symptoms in TNBC patients, enhance immunity, reduce recurrence and metastasis, and prolong disease-free survival. However, clinical evidence regarding its efficacy in enhancing the therapeutic effect of neoadjuvant chemotherapy for TNBC remains to be established. OBJECTIVE This study aims to analyze the impact of SLLXG on the efficacy of neoadjuvant chemotherapy for TNBC, evaluate its synergistic effect on neoadjuvant chemotherapy, and identify potential beneficiary populations for SLLXG in treating TNBC. It seeks to establish a standardized diagnostic and treatment protocol for broader clinical implementation. METHODS This study enrolled 306 patients diagnosed with TNBC. Patients were randomly assigned to two groups: one receiving neoadjuvant chemotherapy combined with SLLXG treatment, and the other receiving neoadjuvant chemotherapy combined with SLLXG placebo treatment. The primary efficacy endpoint was pathological complete response rate (pCR). Secondary efficacy endpoints included objective remission rate (ORR); clinical benefit rate (CBR); Miller-Payne (MP) staging for breast cancer; residual cancer burden (RCB) assessment; peripheral blood lymphocyte levels; tumor-infiltrating lymphocytes (sTILs) in the tumor region stroma; EORTC Quality of Life Questionnaire QLQ-C30 (V3.0). Evaluation timepoints will occur after completion of cycles 2, 4, 6, and 8 of neoadjuvant chemotherapy. Data will be analyzed using SPSS (version 25.0) to compare within-group and between-group differences between the two cohorts, with a significance level of α=0.05 for hypothesis testing. RESULTS The study protocol was approved by the Medical Ethics Committee in October 2025. Patient recruitment is scheduled to commence in February 2026. As of January 2026, no patients have been enrolled. The study is expected to be completed by June 2027. CONCLUSIONS The findings of this study will validate the efficacy of SLLXG in treating TNBC and confirm its synergistic effect on treatment outcomes compared to neoadjuvant chemotherapy alone. CLINICALTRIAL International Traditional Medicine Clinical Trial Registry: ITMCTR2026000039; http://itmctr.ccebtcm.org.cn/