Feasibility Trial of Electroacupuncture for Aromatase Inhibitor—Related Arthralgia in Breast Cancer Survivors

Abstract

Background. Arthralgia affects postmenopausal women receiving aromatase inhibitors (AIs) for breast cancer. Given the existing evidence for electroacupuncture (EA) for treatment of osteoarthritis in the general population, this study aims to establish the feasibility of studying EA for treating AI-related arthralgia. Patients and Methods. Postmenopausal women with stage I-III breast cancer who reported AI-related arthral gia were enrolled in a single-arm feasibility trial. EA was provided twice a week for 2 weeks followed by 6 weekly treatments. The protocol was based on Chinese medicine diagnosis of “Bi” syndrome with electrostimulation of needles around the painful joint(s). Pain severity of the modified Brief Pain Inventory was used as the primary outcome. Joint stiffness, joint interference, and Patient Global Impression of Change (PGIC) were secondary outcomes. Paired t tests were used for analysis. Results. Twelve women were enrolled and all provided data for analysis. From baseline to the end of intervention, patients reported reduction in pain severity (from 5.3 to 1.9), stiffness (from 6.9 to 2.4), and joint symptom interference (from 4.7 to 0.8), all P < .001; 11/12 considered joint symptoms “very much better” based on the PGIC. Subjects also reported significant decrease in fatigue (from 4.4 to 1.9, P = .005) and anxiety (from 7.1 to 4.8, P = .01). No infection or development or worsening of lymphedema was observed. Conclusion. Preliminary data establish the feasibility of recruitment and acceptance as well as promising preliminary safety and effectiveness. A randomized controlled trial is warranted to establish the efficacy of EA for AI-related arthralgia in breast cancer survivors.

Keywords

acupuncture breast neoplasm clinical trial aromatase inhibitors adverse effects joint diseases

References

Jakesz R. , Jonat W. , Gnant M. , et al. Switching of postmenopausal women with endocrine-responsive early breast cancer to anastrozole after 2 years' adjuvant tamoxifen: combined results of ABCSG trial 8 and ARNO 95 trial. Lancet. 2005;366: 455-462.

Goss PE , Ingle JN , Martino S. , et al. A randomized trial of letrozole in postmenopausal women after five years of tamoxifen therapy for early-stage breast cancer. N Engl J Med. 2003;349: 1793-1802.

Howell A. , Cuzick J. , Baum M. , et al. Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years' adjuvant treatment for breast cancer. Lancet. 2005;365:60-62.

Coombes RC , Hall E. , Gibson LJ , et al. A randomized trial of exemestane after two to three years of tamoxifen therapy in postmenopausal women with primary breast cancer. N Engl J Med. 2004;350:1081-1092.

Crew KD , Greenlee H. , Capodice J. , et al. Prevalence of joint symptoms in postmenopausal women taking aromatase inhibitors for early-stage breast cancer. J Clin Oncol. 2007;25:3877-3883.

Morales L. , Pans S. , Paridaens R. , et al. Debilitating musculoskeletal pain and stiffness with letrozole and exemestane: associated tenosynovial changes on magnetic resonance imaging . Breast Cancer Res Treat. 2007;104:87-91.

Donnellan PP , Douglas SL , Cameron DA , Leonard RC Aromatase inhibitors and arthralgia. J Clin Oncol. 2001;19:2767.

Boon HS , Olatunde F. , Zick SM Trends in complementary/ alternative medicine use by breast cancer survivors: comparing survey data from 1998 and 2005. BMC Womens Health . 2007;7:4.

Mao JJ , Palmer SC , Straton JB , et al. Cancer survivors with unmet needs were more likely to use complementary and alternative medicine. J Cancer Surviv. 2008;2:116-124.

10.

Felson DT , Cummings SR Aromatase inhibitors and the syndrome of arthralgias with estrogen deprivation . Arthritis Rheum. 2005;52:2594-2598.

11.

Han JS Acupuncture and endorphins. Neurosci Lett. 2004;361: 258-261.

12.

Vas J. , Mendez C. , Perea-Milla E. , et al. Acupuncture as a complementary therapy to the pharmacological treatment of osteoarthritis of the knee: randomised controlled trial. BMJ. 2004;329:1216.

13.

Witt C. , Brinkhaus B. , Jena S. , et al. Acupuncture in patients with osteoarthritis of the knee: a randomised trial. Lancet. 2005;366:136-143.

14.

Berman BM , Lao L. , Langenberg P. , Lee WL , Gilpin AM , Hochberg MC Effectiveness of acupuncture as adjunctive therapy in osteoarthritis of the knee: a randomized, controlled trial. Ann Intern Med. 2004;141:901-910.

15.

Langevin HM , Hammerschlag R. , Lao L. , Napadow V. , Schnyer RN , Sherman KJ Controversies in acupuncture research: selection of controls and outcome measures in acupuncture clinical trials. J Altern Complement Med. 2006;12:943-953.

16.

Huang MI , Nir Y. , Chen B. , Schnyer R. , Manber R. A randomized controlled pilot study of acupuncture for postmenopausal hot flashes: effect on nocturnal hot flashes and sleep quality. Fertil Steril. 2006;86:700-710.

17.

Nir Y. , Huang MI , Schnyer R. , Chen B. , Manber R. Acupuncture for postmenopausal hot flashes. Maturitas. 2007;56:383-395.

18.

Schnyer RN , Iuliano D. , Kay J. , Shields M. , Wayne P. Development of protocols for randomized sham-controlled trials of complex treatment interventions: Japanese acupuncture for endometriosisrelated pelvic pain. J Altern Complement Med. 2008;14:515-522.

19.

Anonymous. Essentials of Chinese Acupuncture. Beijing, Peoples Republic of China: Foreign Languages Press; 1993.

20.

Cheng X , ed. Chinese Acupuncture and Moxibustion. Beijing, Peoples Republic of China: Foreign Languages Press; 1987.

21.

Mao JJ , Farrar JT , Armstrong K. , Donahue A. , Ngo J. , Bowman MA De qi: Chinese acupuncture patients' experiences and beliefs regarding acupuncture needling sensation-an exploratory survey. Acupunct Med. 2007;25:158-165.

22.

Han JS , Xie GX , Zhou ZF , Folkesson R. , Terenius L. Enkephalin and beta-endorphin as mediators of electro-acupuncture analgesia in rabbits: an antiserum microinjection study. Adv Biochem Psychopharmacol. 1982;33:369-377.

23.

Cleeland CS , Ryan KM Pain assessment: global use of the Brief Pain Inventory. Ann Acad Med Singapore. 1994;23:129-138.

24.

Sloan JA , Aaronson N. , Cappelleri JC , Fairclough DL , Varricchio C. ; Clinical Significance Consensus Meeting Group. Assessing the clinical significance of single items relative to summated scores. Mayo Clin Proc. 2002;77:479-487.

25.

Mendoza TR , Wang XS , Cleeland CS , et al. The rapid assessment of fatigue severity in cancer patients: use of the Brief Fatigue Inventory. Cancer. 1999;85:1186-1196.

26.

Lin CC , Chang AP , Chen ML , Cleeland CS , Mendoza TR , Wang XS Validation of the Taiwanese version of the Brief Fatigue Inventory. J Pain Symptom Manage. 2006;32:52-59.

27.

Vickers AJ , Straus DJ , Fearon B. , Cassileth BR Acupuncture for postchemotherapy fatigue: a phase II study. J Clin Oncol. 2004;22: 1731-1735.

28.

Zigmond AS , Snaith RP The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983;67:361-370.

29.

Moorey S. , Greer S. , Watson M. , et al. The factor structure and factor stability of the hospital anxiety and depression scale in patients with cancer. Br J Psychiatry . 1991;158:255-259.

30.

Smith AB , Selby PJ , Velikova G. , et al. Factor analysis of the Hospital Anxiety and Depression Scale from a large cancer population. Psychol Psychother. 2002;75(pt 2):165-176.

31.

Sellick SM , Edwardson AD Screening new cancer patients for psychological distress using the hospital anxiety and depression scale. Psychooncology. 2007;16:534-542.

32.

Carpenter JS , Elam JL , Ridner SH , Carney PH , Cherry GJ , Cucullu HL Sleep, fatigue, and depressive symptoms in breast cancer survivors and matched healthy women experiencing hot flashes. Oncol Nurs Forum. 2004;31:591-5598.

33.

Linde K. , Witt CM , Streng A. , et al. The impact of patient expectations on outcomes in four randomized controlled trials of acupuncture in patients with chronic pain. Pain. 2007;128: 264-271.

34.

Mao JJ , Armstrong K. , Farrar JT , Bowman MA Acupuncture expectancy scale: development and preliminary validation in China . Explore (NY). 2007 ;3:372-377.

35.

Lao L. , Berman B. Evaluating the effects of acupuncture on knee osteoarthritis: a stepwise approach to research, University of Maryland experience [in Chinese]. Zhong Xi Yi Jie He Xue Bao. 2005;3:421-425.

36.

Lewith GT , White PJ , Pariente J. Investigating acupuncture using brain imaging techniques: the current state of play. Evid Based Complement Alternat Med. 2005;2:315-319.

37.

Biella G. , Sotgiu ML , Pellegata G. , Paulesu E. , Castiglioni I. , Fazio F. Acupuncture produces central activations in pain regions. Neuroimage. 2001;14(1, pt 1):60-66.

38.

Pariente J. , White P. , Frackowiak RS , Lewith G. Expectancy and belief modulate the neuronal substrates of pain treated by acupuncture. Neuroimage. 2005;25:1161-1167.

39.

Newberg AB , Lariccia PJ , Lee BY , Farrar JT , Lee L. , Alavi A. Cerebral blood flow effects of pain and acupuncture: a preliminary single-photon emission computed tomography imaging study. J Neuroimaging . 2005;15:43-49.

40.

Hui KK , Liu J. , Makris N. , et al. Acupuncture modulates the limbic system and subcortical gray structures of the human brain: evidence from fMRI studies in normal subjects . Hum Brain Mapp. 2000;9:13-25.

41.

Fang JL , Krings T. , Weidemann J. , Meister IG , Thron A. Functional MRI in healthy subjects during acupuncture: different effects of needle rotation in real and false acupoints. Neuroradiology . 2004;46:359-362.

42.

Napadow V. , Makris N. , Liu J. , Kettner NW , Kwong KK , Hui KK Effects of electroacupuncture versus manual acupuncture on the human brain as measured by fMRI. Hum Brain Mapp. 2005;24:193-205.

43.

Wu MT , Sheen JM , Chuang KH , et al. Neuronal specificity of acupuncture response: a fMRI study with electroacupuncture. Neuroimage. 2002;16:1028-1037.

44.

Hui KK , Liu J. , Marina O. , et al. The integrated response of the human cerebro-cerebellar and limbic systems to acupuncture stimulation at ST 36 as evidenced by fMRI. Neuroimage. 2005;27:479-496.

45.

Boutouyrie P. , Corvisier R. , Azizi M. , et al. Effects of acupuncture on radial artery hemodynamics: controlled trials in sensitized and naive subjects. Am J Physiol Heart Circ Physiol. 2001;280: H628-H633.

46.

Litscher G. , Wang L. , Huber E. , Nilsson G. Changed skin blood perfusion in the fingertip following acupuncture needle introduction as evaluated by laser Doppler perfusion imaging. Lasers Med Sci. 2002;17:19-25.

47.

Langevin HM , Yandow JA Relationship of acupuncture points and meridians to connective tissue planes. Anat Rec. 2002 ;269: 257-265.

48.

Langevin HM , Churchill DL , Wu J. , et al. Evidence of connective tissue involvement in acupuncture. FASEB J. 2002;16:872-874.

49.

Langevin HM , Konofagou EE , Badger GJ , et al. Tissue displacements during acupuncture using ultrasound elastography techniques. Ultrasound Med Biol . 2004;30:1173-1183.

50.

Chae Y. , Hong MS , Kim GH , et al. Protein array analysis of cytokine levels on the action of acupuncture in carrageenan-induced inflammation. Neurol Res. 2007;29(suppl 1):S55-S58.

51.

Mao JJ , Stricker CT , Bruner D. , Xie SX , Bowman MA , Farrar JT , Greene BT , DeMichele A. (forthcoming) Patterns and Risk Factors Associated with Aromatase Inhibitor Related Arthralgia among Breast Cancer Survivors. Cancer.