Acupuncture for Aromatase Inhibitor-Related Arthralgias in Breast Cancer Patients

在早期激素受体阳性乳腺癌患者中，第三代芳香化酶抑制剂在改善无病生存率、降低远处和局部复发率以及降低对侧乳腺癌发生率方面优于他莫昔芬。然而，高达50%的接受人工智能治疗的妇女报告出现了使人衰弱的肌肉骨骼疼痛和关节痛的症状，这些症状可能导致不依从性和早期停药，从而影响生存。我们之前的II期随机研究（n=40）表明，与假针灸相比，每周两次针灸，持续6周，可改善人工智能引起的关节疼痛/僵硬，通过改进的简短疼痛指数简表（mBPI-sf）测量，疼痛评分差50%。拟议的SWOG III期随机、假对照、盲法、多中心临床试验将研究针灸对228名I-III期乳腺癌患者开始或增加的关节疼痛/僵硬的影响。女性将从四个机构招募，随机分为真针灸组和假针灸组，每周两次，持续6周，然后每周进行维持性针灸或假针灸，持续6周，或进入等候名单对照组。真正的针灸疗程将由标准化的全身和关节特定穴位处方和NADA耳部协议组成。假针灸治疗将包括全身表面针刺和关节特定的穴位处方，不对应任何真正的穴位。主要假设是，与假针灸相比，每周两次针灸，连续6周，然后每周针灸，连续6周，将减少AI诱导的关节炎妇女的关节疼痛/僵硬，在6周时通过mBPI-SF评分测量。次要终点将评估从第6周到第12周的每周维持真针灸是否能维持第6周的效果（12周时mBPI-SF评分），以及与假针灸相比，真针灸是否能在24周和52周时具有持久的效果（mBPI-SF评分）。其他次要终点（将在基线、6周、12周、24周和52周进行评估）包括1)通过自我管理的问卷（Western Ontario and McMaster university Osteoarthritis， WOMAC）对关节疼痛/僵硬和功能状态进行额外评估；手部慢性类风湿影响评估和量化的改进评分（M-SACRAH）和风湿病临床试验和骨关节炎研究学会国际标准的结果测量（OMERACT-OARSI）， 2)通过自我管理问卷癌症治疗功能评估-乳腺/内分泌亚量表（FACT-B/ES）的生活质量评估，3)镇痛药物的使用，4)功能测试（握力和下肢的“定时起身和行走”）和5)探索性炎症生物标志物和尿液标志物，用于人工智能依从性。这项研究将是第一个大型多中心干预试验，旨在研究针灸对乳腺癌女性人工智能诱导的关节炎的影响。

Third generation aromatase inhibitors have been shown to be superior to tamoxifen in improving disease free survival, decreasing distant and local recurrence rates and decreasing incidence of contra-lateral breast cancer in women with early stage hormone receptor positive breast cancer. However, up to 50% of women on AI report symptoms of debilitating musculoskeletal pain and joint arthralgia that can lead to noncompliance and early discontinuation, thereby impacting survival. Our previous phase II randomized study (n=40) showed that acupuncture administered twice weekly for 6 weeks compare to sham acupuncture improve AI induced joint pain/stiffness as measured by modified Brief Pain Index short form (mBPI-sf) worse pain score by 50%. The proposed SWOG phase III randomized, sham controlled, blinded, multi-centered clinical trial will look at the effects of acupuncture on joint pain/stiffness that started or increased since initiation of AI in 228 women with Stage I-III breast cancer. Women will be recruited from four institutions and randomized to either true acupuncture or sham acupuncture administered twice weekly for 6 weeks follow by maintenance weekly acupuncture or sham acupuncture for 6 weeks or to a wait list control arm. True acupuncture sessions will consists of standardized full body and joint specific point prescription and the NADA auricular protocol. The sham acupuncture treatment will consist of superficial needling at full body and joint specific point prescriptions that do not correspond to any true acupuncture points. The primary hypothesis is that acupuncture administered twice weekly for 6 weeks then weekly for 6 weeks will reduce joint pain/stiffness in women with AI induced arthragia as measured by mBPI-SF scores at 6 weeks compared to sham acupuncture. Secondary endpoints will assess whether weekly maintenance true acupuncture from week 6 to week 12 will maintain the effects seen at week 6 as measured by mBPI-SF score at 12 weeks and whether true acupuncture will have a durable effect as measure by mBPI-SF score at 24 and 52 weeks, compared to sham acupuncture. Other secondary endpoint (to be evaluated at baseline, 6, 12, 24 and 52 weeks) include 1) additional assessment of joint pain/stiffness and functional status via self administered questionnaires (Western Ontario and McMaster Universities Osteoarthritis (WOMAC), Modified Score for the Assessment and Quantification of Chronic Rheumatoid Affections of the Hands (M-SACRAH) and Outcome Measures in Rheumatology Clinical Trials and Osteoarthritis Research Society International criteria (OMERACT-OARSI), 2) quality of life assessment via the self administered questionnaire Functional Assessment of Cancer Therapy-Breast/Endocrine subscale (FACT-B/ES), 3) analgesic use, 4) functional testing (grip strength and ¿timed get up and go¿ for lower extremity¿) and 5) exploratory inflammatory biomarkers and urine markers for AI adherence. This study will be the first large multi-center center intervention trial looking at the effects of acupuncture on AI induced arthragia in women with breast cancer.