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Shenqi Shiyiwei Granule for breast cancer related fatigue-centered symptom cluster: protocol of a multicenter randomized double-blind placebo-controlled trial

Year: 2026

Type: article

Abstract: Background: Breast cancer survivors frequently experience fatigue-centered symptom clusters-concurrent, interrelated symptoms including fatigue, pain, and dyspnea-that significantly impair quality of life and functional status. Despite the high prevalence of these symptoms, few interventional trials have targeted symptom clusters as a unified treatment endpoint. Current management relies predominantly on behavioral interventions with inconsistent efficacy, and no pharmacological agent has demonstrated high-quality evidence for cluster-level symptom control in this population. Methods: This multicenter, randomized, double-blind, placebo-controlled trial will enroll 262 postoperative breast cancer survivors (stage I-IIIA) with moderate-to-severe fatigue-centered symptom clusters from 11 hospitals across China. Eligible participants must have completed adjuvant therapy, exhibit an ECOG performance status of 0-1, and present with a MDASI-C fatigue-dyspnea-pain subscale score ≥4. Participants will be randomized 1:1 to receive either Shenqi Shiyiwei Granule or matching placebo for 60 days, with standardized psycho-exercise-dietary guidance provided to all participants throughout a 120-day study period. The primary endpoint is the change from baseline in the fatigue-dyspnea-pain symptom cluster score at 2 months, assessed using the MD Anderson Symptom Inventory-Chinese version (MDASI-C). Secondary endpoints include quality-of-life measures (MFSI-SF, FACT-B, TCM Spleen Qi Deficiency Scale) and cardiopulmonary functional capacity. Exploratory biomarker analyses will evaluate hypothalamic-pituitary-adrenal axis hormones, cytokine profiles, and gonadal hormone concentrations to elucidate potential mechanisms. Efficacy will be analyzed using mixed-effects models for repeated measures (MMRM) with prespecified sensitivity analyses for missing data assumptions. Discussion: This trial represents one of the first rigorous investigations targeting the fatigue-centered symptom cluster as a unified therapeutic endpoint in breast cancer survivors. By combining traditional Chinese herbal medicine with guideline-endorsed behavioral interventions, this study aims to provide high-quality evidence for a novel multi-target treatment strategy. The exploratory biomarker assessments may illuminate the biological mechanisms underlying symptom cluster interrelationships, establishing a foundation for future mechanistic and interventional research in cancer survivorship care. Clinical trial registration: [https://itmctr.ccebtcm.org.cn/mgt/project/user/user-project-view/0A267E22-1E0A-4A95-99B0-E5964124F203], The International Traditional Medicine Clinical Trial Registry [ITMCTR2025001511].

Source: Frontiers in Oncology

DOI: 10.3389/fonc.2026.1941699