Shenqi Shiyiwei Granule trial to test fatigue symptom clusters in breast cancer survivorsNew trial plans to treat fatigue in breast cancer survivors

BackgroundBreast 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.MethodsThis 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.DiscussionThis 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].