Abstract
Aromatase inhibitors (AIs) are the first-line treatment in women with breast cancer
for total estrogen depletion. Half the treated women may develop pain, and this condition
may therefore be seen as a clinical model of pain related to estrogen deprivation.
In this prospective multicenter study, we classified AI-related pain syndromes and
identified their predictors. A 1-year, prospective, multicenter cohort study, with
6 visits, was carried out on 135 women with early-stage breast cancer and no pain
at the start of AI treatment. At initial assessment, we investigated clinical (demographic
and psychosocial, cancer characteristics and treatment, sleep, quality of life), biological
(sex hormones, vitamin D, bone biomarkers, oxidative stress, immunologic and inflammatory
markers), environmental, and genetic (polymorphism for pain mechanisms) risk factors
for pain. During 1 year of follow-up, 77 women (57%) developed pain, leading to AI
discontinuation in 12 cases. Five pain syndromes were identified: joint pain (36%),
diffuse pain (22%), tendinitis (22%), neuropathic pain (9%), and mixed pain (11%),
which are mostly persistent (57%), with diffuse and joint pains the most intense.
Risk factors for the development of pain included higher levels of anxiety and impaired
quality of life at the initial assessment, whereas cancer characteristics, genetic
background, inflammation, and immunologic and hormonal status at baseline were not
significant predictors.
Perspective
This article presents a classification of AI–related pain syndromes induced by estrogen
deprivation that were previously described as arthralgia, but not as neuropathic,
diffuse, and mixed pain. This estrogen deprivation–related condition represents a
clinical model of pain, and our study identified mostly psychological risk factors
for pain development.
Key words
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to The Journal of PainAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early stage breast cancer: Results of the ATAC (Arimidex, Tamoxifen Alone or in Combination) randomised trial.Lancet. 2002; 359: 2131-2139
- Cancer and Leukemia Group B: Measurement of affective and activity pain interference using the Brief Pain Inventory (BPI): cancer and leukemia group B 70903.Pain Med. 2012; 13: 1417-1424
- The validity of the Hospital Anxiety and Depression Scale. An updated literature review.J Psychosom Res. 2002; 52: 69-77
- Comparison of pain syndromes associated with nervous or somatic lesions and development of a new neuropathic pain diagnostic questionnaire (DN4).Pain. 2005; 114: 29-36
- A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer.N Engl J Med. 2005; 353: 2747-2757
- Sex hormone binding globulin and aging.Horm Metab Res. 2009; 41: 173-182
- Serum sex hormones and severity of osteoarthritis of the hand.J Rheumatol. 1993; 20: 1170-1175
- Breast cancer risk associated with genotype polymorphism of the catechol estrogen-metabolizing genes: A multigenic study on cancer susceptibility.Int J Cancer. 2005; 113: 345-353
- Pain assessment: Global use of the Brief Pain Inventory.Ann Acad Med Singapore. 1994; 23: 129-138
- A psychobiological model of temperament and character.Arch Gen Psychiatry. 1993; 50: 975-990
- The Temperament and Character Inventory (TCI): A Guide to Its Development and Use.Center for Psychobiology of Personality, Washington University, St Louis, MO1994
- Aromatase inhibitor-induced arthralgia: Clinical experience and treatment recommendations.Cancer Treat Rev. 2007; 104: 87-91
- 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
- Prevalence of joint symptoms in postmenopausal women taking aromatase inhibitors for early-stage breast cancer.J Clin Oncol. 2007; 25: 3877-3883
- Current opinion of aromatase inhibitor-induced arthralgia in breast cancer in the UK.Clin Oncol. 2011; 23: 674-680
- Sex Hormone-Binding Globulin (SHBG), estradiol and breast cancer.Mol Cell Endocrinol. 2010; 316: 86-92
- Estimates of cancer incidence and mortality in Europe in 2008.Eur J Cancer. 2010; 46: 765-781
- Genetic variation at the CYP19A1 locus predicts circulating estrogen levels but not breast cancer risk in postmenopausal women.Cancer Res. 2007; 67: 1893-1897
- Measures of adult pain.Arthritis Care Res. 2011; 63: S240-S252
- A prospective study of aromatase inhibitor therapy, vitamin D, C-reactive protein and musculoskeletal symptoms.Breast Cancer Res Treat. 2012; 131: 277-285
- Inflammatory cytokines and aromatase inhibitor-associated musculoskeletal syndrome: A case-control study.Br J Cancer. 2010; 103: 291-296
- Prospective characterization of musculoskeletal symptoms in early-stage breast cancer patients treated with aromatase inhibitors.Breast Cancer Res Treat. 2008; 111: 365-372
- Roles of estrogen in bone loss and arthralgia during aromatase inhibitor treatment.Curr Opin Oncol. 2007; 19: S1-S8
- Genetic predictors for acute experimental cold and heat pain sensitivity in humans.J Med Genet. 2006; 43: e40
- Joint pain with aromatase inhibitors: Abnormal frequency of Sjögren syndrome.J Rheumatol. 2007; 34: 2259-2263
- Patterns and risk factors associated with aromatase inhibitor-related arthralgia among breast cancer survivors.Cancer. 2009; 115: 3631-3639
- Estrogen effects on the brain: actions beyond the hypothalamus via novel mechanisms.Behav Neurosci. 2012; 126: 4-16
- Classification of Chronic Pain.2nd ed. IASP Task Force on Taxonomy, IASP Press, Seattle, WA1994
- IES Steering Committee: 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. 2012; 13: 420-432
- Prospective study to assess short-term intra-articular and tenosynovial changes in the aromatase inhibitor-associated arthralgia syndrome.J Clin Oncol. 2008; 26: 3147-3152
- Rheumatic disorders and functional disability with aromatase inhibitor therapy.Clin Breast Cancer. 2010; 10: 144-147
- Aromatase inhibitors induced arthralgia: A review.Ann Oncol. 2013; 00: 1-7
- The Temperament and Character Inventory–Revised (TCI-R): Psychometric characteristics on the French version.Acta Psychiatr Scand. 2005; 112: 126-133
- Aromatase inhibitor-associated arthralgia and/or bone pain: Frequency and characterization in non-clinical trial patients.Clin Breast Cancer. 2007; 7: 775-778
- A prospective pilot investigating the musculoskeletal pain in breast cancer patients receiving aromatase inhibitor therapy.Curr Oncol. 2011; 18: 285-294
- ATAC Trialists' Group: Risk factors for joint symptoms in patients enrolled in the ATAC trial: A retrospective, exploratory analysis.Lancet Oncol. 2008; 9: 866-872
- Aromatase inhibitor-induced carpal tunnel syndrome: Results from the ATAC trial.J Clin Oncol. 2009; 27: 4961-4965
- Defining the aromatase inhibitor musculoskeletal syndrome: A prospective study.Arthritis Care Res. 2012; 64: 1910-1918
- Effect of baseline serum vitamin D levels on aromatase inhibitor-induced musculoskeletal symptoms: results from the IBIS-II chemoprevention study using anastrozole.Breast Cancer Res Treat. 2012; 132: 625-629
- The Multidimensional Fatigue Inventory (MFI) psychometric qualities of an instrument to assess fatigue.J Psychosom Res. 1995; 39: 315-325
- The European Organization for Research and Treatment of Cancer breast cancer-specific quality-of-life questionnaire module: First results from a three-country field study.J Clin Oncol. 1996; 14: 2756
- The Pain Catastrophizing Scale: Development and validation.Psychol Assess. 1995; 7: 432-524
- Expression of genes for estrogen receptors alpha and beta in human articular chondrocytes.Osteoarthritis Cartilage. 1999; 7: 560-566
- The American College of Rheumatology 1990 criteria for the classification of fibromyalgia: Report of the Multicenter Criteria Committee.Arthritis Rheum. 1990; 33: 160-172
- Natural history of menopause symptoms in primary care patients: A MetroNet Study.J Am Board Fam Pract. 2005; 18: 374-382
Article info
Publication history
Published online: December 23, 2013
Accepted:
November 20,
2013
Received:
September 30,
2013
Footnotes
This study received financial support from the CNP foundation, the APICIL foundation and IUD-Institut Upsa de la Douleur.
None of the authors have any conflicts of interest related to this study.
Identification
Copyright
© 2014 American Pain Society. Published by Elsevier Inc. All rights reserved.
