Nan Peng¹, Xiao-min Wang¹, Ming-wei Yu¹, Guo-wang Yang¹, Qi Fu¹, Jie Yu¹, Qiang Liu², Chen Li¹, Wei-ru Xu¹, Yi Zhang¹, Cong Ma¹, Lin Yang¹, Ren-cun Yu¹ 

¹Department of Oncology, Beijing Hospital of Traditional Chinese Medicine affiliated with Capital Medical University, ²Guidance Centre for Clinical Evidence-Based Research, World Federation of Chinese Medicine Societies

Objective:To evaluate whether the traditional Chinese medicine Yi Shen Jian Gu granules (YSJG) is effective to relieve aromatase inhibitor-associated musculoskeletal symptoms (AIMSS) in patients with breast cancer. Method: This study is a multicenter, randomized, double-blind, placebo-controlled clinical trial with 2 parallel arms. Participants were recruited from three centers: Beijing Hospital of Traditional Chinese Medicine affiliated with Capital Medical University, Beijing Cancer Hospital, and Guang' An Men Hospital affiliated with China Academy of Chinese Medical Sciences. After a 2-week run-in period, eligible participants were randomly assigned to the YSJG group or the placebo group. All participants were taking one of AIs and calcium agent (calcium carbonate and vitamin D3 chewable tablets). The YSJG group received YSJG granules, and the placebo group received placebo granules. Both groups had a 12-week treatment period and a 12-week follow-up period. The primary outcome measure was Brief Pain Inventory-Short Form (BPI-SF), the secondary outcome measures included Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index, the Modified Score for the Assessment and Quantification of Chronic Rheumatoid Affections of the Hands (M-SACRAH), the Functional Assessment of Cancer Therapy breast cancer-specific (FACT-B), and traditional Chinese medicine syndrome scale (TCM scale), which were obtained at baseline and at 4, 8, 12 and 24 weeks. Bone mineral density (BMD), also as a secondary outcome measure, was assessed before and after treatment (at baseline and at 12 weeks). Result: Of 146 participants enrolled, 84 participants were randomly assigned and 73 were evaluable. Baseline characteristics were comparable between two groups. The primary outcome was the differences in mean BPI-SF scores at 12 weeks. The worst pain scores decreased by 3.05 points (49.4%) for YSJG group compared with a 1.60-point decrease (26.8%) for the placebo group (P=0.002). The difference was still found between two groups at 24 weeks (3.24±1.65 vs 4.74±1.92, P<0.001). Significantly improvements were also observed for the WOMAC, M-SACRAH, TCM, and FACT-B scores. However, no significant modulation was seen in BMD after 12-week treatment. Few side effects were reported in either group. YSJG granules was well-tolerated. Conclusion: Patients with AIMSS treated with YSJG granules had significant improvements in musculoskeletal symptoms and quality of life compared with the placebo group. The improvements still retained after treatment. Traditional Chinese medicine, Yi Shen Jian Gu granules, is a safe, effective and well-tolerated strategy for managing AIMSS.

Key Words: breast cancer  aromatase inhibitor-associated musculoskeletal symptoms