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Symptoms: Aromatase Inhibitor Induced Arthralgias

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Improving Outcomes for Breast Cancer Survivors

Part of the book series: Advances in Experimental Medicine and Biology ((BCRF,volume 862))

Abstract

Recent clinical trials have demonstrated that aromatase inhibitors (AIs) are slightly more effective than tamoxifen at reducing breast cancer recurrences. However, breast cancer patients receiving AIs have a higher incidence of musculoskeletal symptoms, particularly joint pain and stiffness. Musculoskeletal pain and stiffness can lead to noncompliance and increased utilization of health care resources. There is a suggestion that the syndrome is the result of estrogen deprivation and may share components with autoimmune diseases such as Sjögren’s syndrome. Several factors may increase the likelihood of developing AI arthralgia, such as prior chemotherapy, prior hormone replacement therapy, and increased weight; there are inconsistencies with regard to the data on genetic predispositions to this syndrome. While several studies have been done to evaluate interventions to treat or prevent AI arthralgia, no clear treatment has emerged as being particularly beneficial. Much of the research has been limited by small sample size, difficulty blinding patients to placebo, inconsistent definitions of the syndrome, multiple patient reported outcomes, lack of objective outcome measures and heterogeneous patient populations. We are at the early stages of research in characterizing, understanding etiology, preventing and treating AI arthralgias; however much work is being done in this area which, hopefully, will ultimately improve the lives of women with breast cancer.

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References

  • Anonymous (1998) NIH consensus conference. Acupuncture. JAMA 280:1518–1524

    Google Scholar 

  • Azria D, Lamy Y, Belkacemi G et al (2007) Letrozole-induced arthralgia: results of a multicenteric prospective trial exploring clinical parameters and plasma biomarkers. ASCO Breast Cancer Symposium

    Google Scholar 

  • Baum M, Budzar AU, Cuzick J (2002) Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: first results of the ATAC randomised trial. Lancet 359:2131–2139 [see comment][erratum appears in Lancet 2002 Nov 9;360(9344):1520]

    Article  CAS  PubMed  Google Scholar 

  • Birrell S, Tilley W (2009) Testosterone undecanoate treatment reduces joint morbidities induced by anastrozole therapy in postmenopausal women with breast cancer: results of a double-blind, randomized phase II trial. San Antonio breast cancer symposium

    Google Scholar 

  • Blanchard O, Tsagris L, Rappaport R et al (1991) Age-dependent responsiveness of rabbit and human cartilage cells to sex steroids in vitro. J Steroid Biochem Mol Biol 40:711–716

    Article  CAS  PubMed  Google Scholar 

  • Briot K, Tubiana-Hulin M, Bastit L et al (2010) Effect of a switch of aromatase inhibitors on musculoskeletal symptoms in postmenopausal women with hormone-receptor-positive breast cancer: the ATOLL (articular tolerance of letrozole) study. Breast Cancer Res Treat 120:127–134

    Article  CAS  PubMed  Google Scholar 

  • Carey TS, Evans A, Hadler N et al (1995) Care-seeking among individuals with chronic low back pain. Spine 20:312–317

    Article  CAS  PubMed  Google Scholar 

  • Chlebowski RT, Cirillo DJ, Eaton CB et al (2013) Estrogen alone and joint symptoms in the women’s health initiative randomized trial. Menopause 20:600–608

    PubMed  Google Scholar 

  • Claassen H, Schluter M, Schunke M et al (2006) Influence of 17beta-estradiol and insulin on type II collagen and protein synthesis of articular chondrocytes. Bone 39:310–317

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  • Crew KD, Capodice J, Greenlee H et al (2010) Randomized, blinded, sham-controlled trial of acupuncture for the management of aromatase inhibitor-associated joint symptoms in women with early stage breast cancer. J Clin Oncol 28:1154–1160

    Article  CAS  PubMed  Google Scholar 

  • Cuzick J, Sestak I, Cella D et al (2008) Treatment-emergent endocrine symptoms and the risk of breast cancer recurrence: a retrospective analysis of the ATAC trial. Lancet Oncol 9:1143–1148

    Article  CAS  PubMed  Google Scholar 

  • Dayani N, Corvol MT, Robel P et al (1988) Estrogen receptors in cultured rabbit articular chondrocytes: influence of age. J Steroid Biochem 31:351–356

    Article  CAS  PubMed  Google Scholar 

  • DeSantis C, Ma J, Bryan L et al (2014) Breast cancer statistics, 2013. CA Cancer J Clin 64:52–62

    Article  PubMed  Google Scholar 

  • Dizdar O, Ozcakar L, Malas FU et al (2009) Sonographic and electrodiagnostic evaluations in patients with aromatase inhibitor-related arthralgia. J Clin Oncol 27:4955–4960

    Article  PubMed  Google Scholar 

  • Dougherty RH, Rohrer JL, Hayden D et al (2005) Effect of aromatase inhibition on lipids and inflammatory markers of cardiovascular disease in elderly men with low testosterone levels. Clin Endocrinol (Oxf) 62:228–235

    Article  CAS  Google Scholar 

  • Galantino ML, Callens ML, Cardena GJ et al (2013) Tai chi for well-being of breast cancer survivors with aromatase inhibitor-associated arthralgias: a feasibility study. Altern Ther Health Med 19:38–44

    PubMed  Google Scholar 

  • Garcia-Giralt N, Rodriguez-Sanz M, Prieto-Alhambra D et al (2013) Genetic determinants of aromatase inhibitor-related arthralgia: the B-ABLE cohort study. Breast Cancer Res Treat 140:385–395

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Goss PE, Ingle JN, Martino S et al (2005) Randomized trial of letrozole following tamoxifen as extended adjuvant therapy in receptor-positive breast cancer: updated findings from NCIC CTG MA.17. J Natl Cancer Inst 97:1262–1271

    Article  CAS  PubMed  Google Scholar 

  • Greenlee H, Crew KD, Shao T et al (2013) Phase II study of glucosamine with chondroitin on aromatase inhibitor-associated joint symptoms in women with breast cancer. Support Care Cancer 21:1077–1087

    Article  PubMed  Google Scholar 

  • Guerne PA, Carson DA, Lotz M (1990) IL-6 production by human articular chondrocytes. Modulation of its synthesis by cytokines, growth factors, and hormones in vitro. J Immunol 144:499–505

    CAS  PubMed  Google Scholar 

  • Hadji P, Kieback DG, Tams J et al (2012) Correlation of treatment-emergent adverse events and clinical response to endocrine therapy in early breast cancer: a retrospective analysis of the German cohort of TEAM. Ann Oncol 23:2566–2572

    Article  CAS  PubMed  Google Scholar 

  • Hadji P, Jackisch C, Bolten W et al (2014) COMPliance and arthralgia in clinical therapy: the COMPACT trial, assessing the incidence of arthralgia, and compliance within the first year of adjuvant anastrozole therapy. Ann Oncol 25:372–377

    Article  CAS  PubMed  Google Scholar 

  • Harputluoglu H, Dizdar O, Malas U et al (2008) Aromatase inhibitor-associated arthralgia: prevalence, clinical and serum parameters among Turkish postmenopausal breast cancer patients. ASCO Annual Meeting. J Clin Oncol (May 20 supplement)

    Google Scholar 

  • Henry NL, Giles JT, Ang D et al (2008) Prospective characterization of musculoskeletal symptoms in early stage breast cancer patients treated with aromatase inhibitors. Breast Cancer Res Treat 111:365–372

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Henry NL, Banerjee M, Wicha M et al (2011) Pilot study of duloxetine for treatment of aromatase inhibitor-associated musculoskeletal symptoms. Cancer 117:5469–5475

    Article  CAS  PubMed  Google Scholar 

  • Henry NL, Azzouz F, Desta Z et al (2012) Predictors of aromatase inhibitor discontinuation as a result of treatment-emergent symptoms in early-stage breast cancer. J Clin Oncol 30:936–942

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Henry NL, Conlon A, Kidwell KM et al (2014) Effect of estrogen depletion on pain sensitivity in aromatase inhibitor-treated women with early-stage breast cancer. J Pain 15:468–475

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Hershman D, Unger J, Crew K et al (2014) Omega-3 fatty acids for aromatase inhibitor–induced musculoskeletal symptoms in women with early-stage breast cancer (SWOG S0927)

    Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Irwin M, Cartmel B, Gross C et al (2013) Effect of exercise vs. usual care on aromatase inhibitor-associated arthralgias in women with early stage breast cancer: the hormones and physical exercise (HOPE) Study. SABCS

    Google Scholar 

  • Kewman DG, Vaishampayan N, Zald D et al (1991) Cognitive impairment in musculoskeletal pain patients. Int J Psychiatry Med 21:253–262

    Article  CAS  PubMed  Google Scholar 

  • Khan QJ, Reddy PS, Kimler BF et al (2010) Effect of vitamin D supplementation on serum 25-hydroxy vitamin D levels, joint pain, and fatigue in women starting adjuvant letrozole treatment for breast cancer. Breast Cancer Res Treat 119(1):111–118

    Google Scholar 

  • Khan Q, Kimler B, Reddy P et al (2012) Randomized trial of vitamin D3 to prevent worsening of musculoskeletal symptoms and fatigue in women with breast cancer starting adjuvant letrozole: the VITAL trial. J Clin Oncol 30(suppl; abstr 9000)

    Google Scholar 

  • Kubo M, Onishi H, Kuroki S et al (2012) Short-term and low-dose prednisolone administration reduces aromatase inhibitor-induced arthralgia in patients with breast cancer. Anticancer Res 32:2331–2336

    CAS  PubMed  Google Scholar 

  • Laroche M, Borg S, Lassoued S et al (2007) Joint pain with aromatase inhibitors: abnormal frequency of Sjogren’s syndrome. J Rheumatol 34:2259–2263

    CAS  PubMed  Google Scholar 

  • Laroche F, Coste J, Medkour T et al (2014) Classification of and risk factors for estrogen deprivation pain syndromes related to aromatase inhibitor treatments in women with breast cancer: a prospective multicenter cohort study. J Pain 15:293–303

    Article  CAS  PubMed  Google Scholar 

  • Lintermans A, Van Calster B, Van Hoydonck M et al (2011) Aromatase inhibitor-induced loss of grip strength is body mass index dependent: hypothesis-generating findings for its pathogenesis. Ann Oncol 22:1763–1769

    Article  CAS  PubMed  Google Scholar 

  • Mao JJ, Su HI, Feng R et al (2011) Association of functional polymorphisms in CYP19A1 with aromatase inhibitor associated arthralgia in breast cancer survivors. Breast Cancer Res 13:R8

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Mao JJ, Xie SX, Farrar JT et al (2014) A randomised trial of electro-acupuncture for arthralgia related to aromatase inhibitor use. Eur J Cancer 50:267–276

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Mieog JS, Morden JP, Bliss JM et al (2012) Carpal tunnel syndrome and musculoskeletal symptoms in postmenopausal women with early breast cancer treated with exemestane or tamoxifen after 2-3 years of tamoxifen: a retrospective analysis of the intergroup exemestane study. Lancet Oncol 13:420–432

    Article  PubMed  Google Scholar 

  • Morales L, Pans S, Verschueren K et al (2008) Prospective study to assess short-term intra-articular and tenosynovial changes in the aromatase inhibitor-associated arthralgia syndrome. J Clin Oncol 26:3147–3152

    Article  PubMed  Google Scholar 

  • Niravath P (2013) Aromatase inhibitor-induced arthralgia: a review. Ann Oncol 24:1443–1449

    Article  CAS  PubMed  Google Scholar 

  • Oh B, Kimble B, Costa DS et al (2013) Acupuncture for treatment of arthralgia secondary to aromatase inhibitor therapy in women with early breast cancer: pilot study. Acupunct Med 31:264–271

    Article  CAS  PubMed  Google Scholar 

  • Richette P, Corvol M, Bardin T (2003) Estrogens, cartilage, and osteoarthritis. Joint Bone Spine 70:257–262

    Article  PubMed  Google Scholar 

  • Richmond RS, Carlson CS, Register TC et al (2000) Functional estrogen receptors in adult articular cartilage: estrogen replacement therapy increases chondrocyte synthesis of proteoglycans and insulin-like growth factor binding protein 2. Arthritis Rheum 43:2081–2090

    Article  CAS  PubMed  Google Scholar 

  • Riggs BL, Melton LJ 3rd (1992) The prevention and treatment of osteoporosis. N Engl J Med 327:620–627 [see comment][erratum appears in N Engl J Med. 1993 Jan 7;328(1):65; author reply 66; PMID: 8416278]

    Article  CAS  PubMed  Google Scholar 

  • Rosner IA, Manni A, Malemud CJ et al (1982) Estradiol receptors in articular chondrocytes. Biochem Biophys Res Commun 106:1378–1382

    Article  CAS  PubMed  Google Scholar 

  • Scudds RJ, Mc DRJ (1998) Empirical evidence of the association between the presence of musculoskeletal pain and physical disability in community-dwelling senior citizens. Pain 75:229–235

    Article  CAS  PubMed  Google Scholar 

  • Sestak I, Cuzick J, Sapunar F et al (2008) Risk factors for joint symptoms in patients enrolled in the ATAC trial: a retrospective, exploratory analysis. Lancet Oncol 9:866–872

    Article  PubMed  Google Scholar 

  • Sestak I, Sapunar F, Cuzick J (2009) Aromatase inhibitor-induced carpal tunnel syndrome: results from the ATAC trial. J Clin Oncol 27:4961–4965

    Article  CAS  PubMed  Google Scholar 

  • Sherwin BB (1996) Hormones, mood, and cognitive functioning in postmenopausal women. Obstet Gynecol 87

    Google Scholar 

  • Shi Q, Giordano SH, Lu H et al (2013) Anastrozole-associated joint pain and other symptoms in patients with breast cancer. J Pain 14:290–296

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Thurlimann B, Keshaviah A, Coates AS et al (2005) A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer. N Engl J Med 353:2747–2757

    Article  PubMed  Google Scholar 

  • Ushiyama T, Inoue K, Nishioka J (1995) Expression of estrogen receptor related protein (p29) and estradiol binding in human arthritic synovium. J Rheumatol 22:421–426

    CAS  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Medicine and Epidemiology, Herbert Irving Comprehensive Cancer Center, Columbia University, 161 Fort Washington, 1068, New York, NY, 10032, USA

    Dawn L. Hershman (Associate Professor)

  2. Breast Cancer Research, Division of Medical Oncology, Rochester, MN, USA

    Charles Loprinzi (Regis Professor)

  3. Medicine & Medical/Molecular Genetics, Indiana University Simon Cancer Center, Indianapolis, IN, USA

    Bryan P. Schneider (Associate Professor)

Authors
  1. Dawn L. Hershman
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  2. Charles Loprinzi
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  3. Bryan P. Schneider
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Corresponding author

Correspondence to Dawn L. Hershman .

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Editors and Affiliations

  1. Distinguished Professor of Health Policy & Management and Medicine, Director, Cancer Prevention & Control Research, UCLA Fielding School of Public Health, David Geffen School of Medicine at UCLA, Jonsson Comprehensive Cancer Center, Los Angeles, California, USA

    Patricia A. Ganz

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© 2015 Breast Cancer Research Foundation

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Hershman, D.L., Loprinzi, C., Schneider, B.P. (2015). Symptoms: Aromatase Inhibitor Induced Arthralgias. In: Ganz, P. (eds) Improving Outcomes for Breast Cancer Survivors. Advances in Experimental Medicine and Biology(), vol 862. Springer, Cham. https://doi.org/10.1007/978-3-319-16366-6_7

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