Prevalence of aromatase inhibitor-induced arthralgia in breast cancer: a systematic review and meta-analysis
- 895 Downloads
Although aromatase inhibitors have proven to be an effective treatment of hormone receptor-positive breast cancer in postmenopausal women, aromatase inhibitor-induced arthralgia (AIA) is an adverse event associated with low compliance with treatment. The aim of this literature study is to assess the prevalence of AIA and to provide an overview of significant predictors for the development of AIA.
A systematic review was conducted using PubMed, Cochrane Library and Web of Science. A meta-analysis was performed and heterogeneity has been investigated by moderator analyses. The meta-analysis was repeated with studies that were considered as best evidence, i.e. studies with an above-average score on the STROBE checklist.
Twenty-one studies (13,177 participants) were included. Prevalence rates ranged from 0.200 to 0.737. Meta-analysis resulted in a pooled estimate of 0.459 (95% CI = [0.397–0.520) with a high heterogeneity (I 2 = 98%). Moderator analysis showed no differences regarding heterogeneity. Predictors for the development of AIA included a body mass index of 25–30 kg/m2 (OR = 0.33), taxane-based chemotherapy (OR = 4.08), stage III cancer (OR = 0.32) and a duration of menopause of 5–10 years (OR = 1.10) or >10 years (OR = 0.44–3.29) (An OR <1 indicates a predictor of lower risk of AIA).
Despite the established benefits of AI, an important portion of the patients experiences AIA. More research is needed to investigate the efficacy of treatments such as exercise therapy for AIA.
KeywordsPrevalence Breast cancer Arthralgia Aromatase inhibitor
Compliance with ethical standards
No funding was received to conduct this systematic review with meta-analysis.
- 1.Boyle P, LB; (2008) World Cancer Report 2008 World Health Organization, International agency for research on CancerGoogle Scholar
- 2.Ferlay J SI, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. (2015) Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J CancerGoogle Scholar
- 3.Stewart B, WC; (2014) World Cancer Report 2014Google Scholar
- 4.Wildiers H, Stordeur S, Vlayen J, Scholten R, Van de Wetering F, Bourgain C, Carly B, Christiaans M, Coquyt V, Lifrange E, Schobbens J-C, van Goethem M, Villeirs G, van Limbergen E, Neven P (2013) Breast cancer in women: diagnosis, treatment and follow-up. Belgian health care knowledge centerGoogle Scholar
- 6.Howell A, Cuzick J, Baum M, Buzdar A, Dowsett M, Forbes JF, Hoctin-Boes G, Houghton I, Locker GY, Tobias JS, Grp AT (2005) Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years' adjuvant treatment for breast cancer. Lancet 365:60–62CrossRefPubMedGoogle Scholar
- 7.Coates AS, Keshaviah A, Thuerlimann B, Mouridsen H, Mauriac L, Forbes JF, Paridaens R, Castiglione-Gertsch M, Gelber RD, Colleoni M, Lang I, Del Mastro L, Smith I, Chirgwin J, Nogaret J-M, Pienkowski T, Wardley A, Jakobsen EH, Price KN, Goldhirsch A (2007) Five years of letrozole compared with tamoxifen as initial adjuvant therapy for postmenopausal women with endocrine-responsive early breast cancer: update of study BIG 1-98. J Clin Oncol 25:486–492CrossRefPubMedGoogle Scholar
- 8.Stearns V, Chapman JA, Ma CX, Ellis MJ, Ingle JN, Pritchard KI, Budd GT, Rabaglio M, Sledge GW, Le Maitre A, Kundapur J, Liedke PE, Shepherd LE, Goss PE (2015) Treatment-associated musculoskeletal and vasomotor symptoms and relapse-free survival in the NCIC CTG MA.27 adjuvant breast cancer aromatase inhibitor trial. J Clin Oncol 33:265–271CrossRefPubMedGoogle Scholar
- 10.Crew KD, Greenlee H, Capodice J, Raptis G, Brafman L, Fuentes D, Sierra A, Hershman DL (2007) Prevalence of joint symptoms in postmenopausal women taking aromatase inhibitors for early-stage breast cancer. Journal of clinical oncology: official journal of the American Society of Clinical Oncology 25:3877–3883CrossRefGoogle Scholar
- 16.Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP, Clarke M, Devereaux PJ, Kleijnen J, Moher D (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ 339:b2700CrossRefPubMedPubMedCentralGoogle Scholar
- 18.Elmagarmid A FZ, Hammady H, Ilyas I, Khabsa M, Ouzzani M (2014) Rayyan: a systematic reviews web app for exploring and filtering searches for eligible studies for Cochrane Reviews Evidence-Informed Publich HealthGoogle Scholar
- 19.Maunsell E GP, Chlebowski RT, Ingle JN, Alés-Martínez JE, Sarto GE, Fabian CJ, Pujol P, Ruiz A, Cooke AL, Hendrix S, Thayer DW, Rowland KM, Dubé P, Spadafora S, Pruthi S, Lickley L, Ellard SL, Cheung AM, Wactawski-Wende J, Gelmon KA, Johnston D, Hiltz A, Brundage M, Pater JL, Tu D, Richardson H (2014) Quality of life in MAP.3 (Mammary Prevention 3): a randomized, placebo-controlled trial evaluating exemestane for prevention of breast cancer. J Clin OncolGoogle Scholar
- 20.Kaufman J (2011) Data extraction and assessment form—templateGoogle Scholar
- 21.von Elm E AD, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP (2008) The strengthening the reporting of observational studies in epidemiology (STROBE)statement: guidelines for reporting observational studies. J Clin EpidemiolGoogle Scholar
- 22.Wallace D, Trikalinos, Lau, Trow, Schmid (2012) Closing the gap between methodologists and end-users: R as a computational back-end. Journal of statistical softwareGoogle Scholar
- 23.DerSimonian R, Laird N (1986) Meta-analysis in clinical trials Controlled clinical trials 7: 177–188Google Scholar
- 24.Higgins JPT GS (2011) Cochrane handbook for systematic reviews of interventions version 5.1.0 [updated March 2011] The Cochrane Collaboration, 2011Google Scholar
- 30.Oberguggenberger A, Hubalek M, Sztankay M, Meraner V, Beer B, Oberacher H, Giesinger J, Kemmler G, Egle D, Gamper E-M, Sperner-Unterweger B, Holzner B (2011) Is the toxicity of adjuvant aromatase inhibitor therapy underestimated? Complementary information from patient-reported outcomes (PROs). Breast Cancer Res Treat 128:553–561CrossRefPubMedGoogle Scholar
- 34.Yagata H, Ohtsu H, Komoike Y, Saji S, Takei H, Nakamura T, Ohashi Y, Iwase T, Shimozuma K (2015) Joint symptoms and health-related quality of life in postmenopausal women with breast cancer who completed 5 years of anastrozole Support Care CancerGoogle Scholar
- 35.Egawa C, Hirokaga K, Takao S, Yamagami K, Miyashita M, Baba M, Ichii S, Konishi M, Kikawa Y, Minohata J, Okuno T, Miyauchi K, Wakita K, Suwa H, Hashimoto T, Nishino M, Matsumoto T, Hidaka T, Konishi Y, Sakoda Y, Miya A, Mitsunobu M, Nishikawa H, Kono S, Kokufu I, Sakita I, Kitatsuji K, Oh K, Miyoshi Y (2015) Risk factors for joint symptoms in postmenopausal Japanese breast cancer patients treated with anastrozole: a prospective multicenter cohort study of patient-reported outcomes International journal of clinical oncologyGoogle Scholar
- 36.Hadji P, Jackisch C, Bolten W, Blettner M, Hindenburg HJ, Klein P, Koenig K, Kreienberg R, Rief W, Wallwiener D, Zaun S, Harbeck N (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 25:372–377CrossRefPubMedGoogle Scholar
- 38.Laroche F, Coste J, Medkour T, Cottu PH, Pierga J-Y, Lotz J-P, Beerblock K, Tournigand C, Decleves X, de Cremoux P, Bouhassira D, Perrott S (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. Journal of Pain 15:293–303CrossRefPubMedGoogle Scholar
- 44.Magliano (2010) Menopausal arthralgia: fact or fiction. Maturitas 67Google Scholar
- 45.Watt (2016 ) Hand osteoarthritis, menopause and menopausal hormone therapy. Maturitas 83Google Scholar
- 47.Lefebvre C, Manheimer E, Glanville J (2011) Chapter 6: searching for studies. In: Higgins JPT, S G (eds) Cochrane handbook for systematic reviews of interventions version 510 (updated March 2011)Google Scholar
- 53.Morales L, Pans S, Paridaens R, Westhovens R, Timmerman D, Verhaeghe J, Wildiers H, Leunen K, Amant F, Berteloot P, Smeets A, Van Limbergen E, Weltens C, Van den Bogaert W, De Smet L, Vergote I, Christiaens MR, Neven P (2007) Debilitating musculoskeletal pain and stiffness with letrozole and exemestane: associated tenosynovial changes on magnetic resonance imaging. Breast Cancer Res Treat 104:87–91CrossRefPubMedGoogle Scholar
- 56.Yang GS, Kim HJ, Griffith KA, Zhu S, Dorsey SG, Renn CL (2016) Interventions for the treatment of aromatase inhibitor-associated arthralgia in breast cancer survivors: a systematic review and meta-analysis Cancer NursGoogle Scholar
- 58.Irwin ML, Cartmel B, Gross CP, Ercolano E, Li F, Yao X, Fiellin M, Capozza S, Rothbard M, Zhou Y, Harrigan M, Sanft T, Schmitz K, Neogi T, Hershman D, Ligibel J (2015) Randomized exercise trial of aromatase inhibitor-induced arthralgia in breast cancer survivors. J Clin Oncol 33:1104–1111CrossRefPubMedGoogle Scholar
- 60.Nijs J, Torres-Cueco R, van Wilgen CP, Girbes EL, Struyf F, Roussel N, van Oosterwijck J, Daenen L, Kuppens K, Vanwerweeen L, Hermans L, Beckwee D, Voogt L, Clark J, Moloney N, Meeus M (2014) Applying modern pain neuroscience in clinical practice: criteria for the classification of central sensitization pain. Pain physician 17:447–457PubMedGoogle Scholar
- 61.Nijs J, Leysen L, Adriaenssens N, Aguilar Ferrandiz ME, Devoogdt N, Tassenoy A, Ickmans K, Goubert D, van Wilgen CP, Wijma AJ, Kuppens K, Hoelen W, Hoelen A, Moloney N, Meeus M (2016) Pain following cancer treatment: guidelines for the clinical classification of predominant neuropathic, nociceptive and central sensitization pain. Acta oncologica (Stockholm, Sweden) 55:659–663CrossRefGoogle Scholar
- 62.Schiavon G, SI; (2014) Status of adjuvant endocrine therapy for breast cancer Breast Cancer ResearchGoogle Scholar