Aromatase inhibitor-associated arthralgia in breast cancer: etiopathogenesis and treatment
- 作者: Shaykhelislamova L.F.1, Lazakovich A.A.1, Vats A.B.1, Akhmedov R.M.1, Zhurov A.S.1, Zueva D.S.1, Belousov A.M.1, Dashyan G.A.1
-
隶属关系:
- N.I. Pirogov Clinic of High Medical Technologies, Saint Petersburg State University
- 期: 卷 32, 编号 6 (2025)
- 页面: 166-172
- 栏目: Oncology
- URL: https://journals.eco-vector.com/2073-4034/article/view/695537
- DOI: https://doi.org/10.18565/pharmateca.2025.6.166-172
- ID: 695537
如何引用文章
详细
Background: Aromatase inhibitors (AIs) are currently used for the chemoprevention and treatment of hormone-dependent (HR+) breast cancer (BC). In premenopausal women with HR+ BC at high risk of recurrence, as determined by clinicopathological characteristics, the use of these drugs reduces the risk by 10–15%.
Objective: Review of literature on the incidence and mechanisms of AI-associated arthralgia, as well as methods for preventing musculoskeletal disorders (MSDs) during treatment with these medications.
Results: The studies reviewed in this study demonstrate that over 50% of women experience pain, necessitating further investigation of the underlying mechanisms of these complications and the development of strategies to minimize them. CDK4/6 inhibitors may be an alternative, as they have less pronounced side effects on the musculoskeletal system. Observations also confirm a link between side effects and recurrence rates. Duloxetine has been shown to be effective in reducing the incidence of arthralgia, although its effect in patients with a high body mass index requires further analysis. The risk of osteoporosis associated with AI treatment can be reduced with bisphosphonates, which is also supported by a reduction in fracture rates in high-risk patients. True acupuncture is an effective method for reducing arthralgia associated with AI use in women with HR+ BC. Moderate physical activity is an effective non-pharmacological strategy for relieving arthralgia during AI therapy in BC, associated with a reduction in systemic inflammation and an improvement in quality of life.
全文:
作者简介
Lyaysan Shaykhelislamova
N.I. Pirogov Clinic of High Medical Technologies, Saint Petersburg State University
Email: shaykhelislamovalf@mail.ru
ORCID iD: 0000-0001-9623-3877
SPIN 代码: 2166-8716
Oncologist, Plastic Surgeon, Oncology Department No. 1
俄罗斯联邦, Saint PetersburgAlina Lazakovich
N.I. Pirogov Clinic of High Medical Technologies, Saint Petersburg State University
Email: shaykhelislamovalf@mail.ru
ORCID iD: 0009-0007-3112-8081
SPIN 代码: 6144-1590
Oncologist, Oncology Department No. 1
俄罗斯联邦, Saint PetersburgAnna Vats
N.I. Pirogov Clinic of High Medical Technologies, Saint Petersburg State University
Email: shaykhelislamovalf@mail.ru
ORCID iD: 0009-0000-0450-0166
Oncologist, Plastic Surgeon, Oncology Department No. 1
俄罗斯联邦, Saint PetersburgRuslan Akhmedov
N.I. Pirogov Clinic of High Medical Technologies, Saint Petersburg State University
Email: shaykhelislamovalf@mail.ru
ORCID iD: 0000-0003-3348-4251
SPIN 代码: 5361-5059
Oncologist, Plastic Surgeon, Oncology Department No. 1
俄罗斯联邦, Saint PetersburgAlexander Zhurov
N.I. Pirogov Clinic of High Medical Technologies, Saint Petersburg State University
Email: shaykhelislamovalf@mail.ru
ORCID iD: 0009-0004-7511-2952
Oncologist, Oncology Department No. 1
俄罗斯联邦, Saint PetersburgDaria Zueva
N.I. Pirogov Clinic of High Medical Technologies, Saint Petersburg State University
Email: shaykhelislamovalf@mail.ru
ORCID iD: 0000-0002-3515-6676
Therapist, Oncology Department No. 1
俄罗斯联邦, Saint PetersburgAlexander Belousov
N.I. Pirogov Clinic of High Medical Technologies, Saint Petersburg State University
Email: shaykhelislamovalf@mail.ru
ORCID iD: 0000-0002-2274-8170
SPIN 代码: 2842-7325
Dr. Sci. (Med.), Surgeon, Oncologist, Deputy Director for Medicine (Surgery and Oncology)
俄罗斯联邦, Saint PetersburgGarik Dashyan
N.I. Pirogov Clinic of High Medical Technologies, Saint Petersburg State University
编辑信件的主要联系方式.
Email: shaykhelislamovalf@mail.ru
ORCID iD: 0000-0001-6183-9764
SPIN 代码: 6989-7148
Dr. Sci. (Med.), Oncologist, Head of Oncology Department No. 1
俄罗斯联邦, Saint Petersburg参考
- Pagani O., Francis P.A., Fleming G.F., et al. Absolute Improvements in Freedom From Distant Recurrence to Tailor Adjuvant Endocrine Therapies for Premenopausal Women: Results From TEXT and SOFT. J Clin Oncol. 2020;38(12):1293–303. https://dx.doi.org/10.1200/JCO.18.01967
- Condorelli R., Vaz-Luis I. Managing side effects in adjuvant endocrine therapy for breast cancer. Expert Rev Anticancer Ther. 2018;18(11):1101–12. https://dx.doi.org/10.1080/14737140.2018.1520096
- Hyder T., Marino C.C., Ahmad S., et al. Aromatase Inhibitor-Associated Musculoskeletal Syndrome: Understanding Mechanisms and Management. Front Endocrinol (Lausanne). 2021;12:713700. doi: 10.3389/fendo.2021.713700
- Korani M. Aromatase inhibitors in male: A literature review. Med Clín Práct. 2023;6(1):100356. https://dx.doi.org/10.1016/j.mcpsp.2022.100356
- Caneiro J.P., Bunzli S., O’Sullivan P. Beliefs about the body and pain: the critical role in musculo-skeletal pain management. Brazil J Phys Ther. 2021;25(1):17–29. doi: 10.1016/j.bjpt.2020.06.003
- Lapidari P., Lustberg M., Havas J., et al. Development and validation of a predictive model of aromatase inhibitor musculoskeletal toxicity among patients with early breast cancer. Ann Oncol. 2024;35(Suppl. 1078–9).
- Francis P.A., Pagani O., Fleming G.F., et al. Tailoring Adjuvant Endocrine Therapy for Premeno-pausal Breast Cancer. N Engl J Med. 2018;379(2):122–37. https://dx.doi.org/10.1056/NEJMoa1803164
- Shapiro C.L. Osteoporosis: A Long-Term and Late-Effect of Breast Cancer Treatments. Cancers. 2020;12(11):3094. https://dx.doi.org/10.3390/cancers12113094
- Bell S.G., Dalton L., McNeish B.L., et al. Aromatase inhibitor use, side effects and discontinuation rates in gynecologic oncology patients. Gynecol Oncol. 2020;159(2):509–14. https://dx.doi.org/10.1016/j.ygyno.2020.08.015
- Borrie A.E., Rose F.A., Choi Y.H., et al. Genetic and Clinical Predictors of Arthralgia During Letrozole or Anastrozole Therapy in Breast Cancer Patients. Breast Cancer Res Treat. 2020;183(2):365–72. https://dx.doi.org/10.1007/s10549-020-05777-1
- Chien H.C., Kao Yang Y.H., Kwoh C.K., et al. Aromatase inhibitors and risk of arthritis and carpal tunnel syndrome among Taiwanese women with breast cancer: a nationwide claims data analysis. J Clin Med. 2020;9(2):566. https://dx.doi.org/10.3390/jcm9020566.
- Asthana R., Zhang L., Wan B.A., et al. Pain descriptors of taxane acute pain syndrome (TAPS) in breast cancer patients - a prospective clinical study. Support Care Cancer. 2020;28(2):589–98. doi: 10.1007/s00520-019-04845-7
- Andrikopoulou A., Fiste O., Liontos M., et al. Aromatase and CDK4/6 inhibitor-induced musculo-skeletal symptoms: a systematic review. Cancers. 2021;13(3):465. https://dx.doi.org/10.3390/cancers13030465
- Yoo T.K., Jang M.J., Lee E., et al. Endocrine treatment-related symptoms and patient outcomes in breast cancer: a meta-analysis. J Breast Cancer. 2018;21(1):37–44. https://dx.doi.org/10.4048/jbc.2018.21.1.37
- De Placido S., Gallo C., De Laurentiis M., et al. Adjuvant anastrozole versus exemestane versus letrozole, upfront or after 2 years of tamoxifen, in endocrine-sensitive breast cancer (FATA-GIM3): a randomised, phase 3 trial. The Lancet Oncology. 2018;19(4):474–85. https://dx.doi.org/10.1016/S1470-2045(18)30116-5
- Tenti S., Correale P., Cheleschi S., et al. Aromatase inhibitors-induced musculoskeletal disorders: current knowledge on clinical and molecular aspects. Int J Mol Sci. 2020;21(16):5625. doi: 10.3390/ijms21165625
- Xu X., Li X., Liang Y., et al. Estrogen modulates cartilage and subchondral bone remodeling in an ovariectomized rat model of postmenopausal osteoarthritis. Med Sci Monitor. 2019;25:3146–53. https://dx.doi.org/10.12659/MSM.916254
- Romero S.A.D., Su H.I., Satagopan J., et al. Clinical and genetic risk factors for aromatase inhibitor-associated arthralgia in breast cancer survivors. Breast. 2020;49:48–54. https://dx.doi.org/10.1016/j.breast.2019.10.008
- Umamaheswaran G., Kadambari D., Muthuvel S.K., et al. Polymorphisms of T-cell leukemia 1A gene loci are not related to the development of adjuvant letrozole-induced adverse events in breast cancer. PLoS One. 2021;16(3):e0247989. doi: 10.1371/journal.pone.0247989
- Cathcart-Rake E., Novotny P., Leon-Ferre R., et al. A randomized, double-blind, placebo-controlled trial of testosterone for treatment of postmenopausal women with aromatase inhibitor-induced arthral-gias: alliance study A221102. Support Care Cancer. 2021;29(1):387–96. https://dx.doi.org/10.1007/s00520-020-05473-2
- Henry N.L., Unger J.M., Schott A.F., et al. Randomized, multicenter, placebo-controlled clinical trial of duloxetine versus placebo for aromatase inhibitor-associated arthralgias in early-stage breast cancer: SWOG S1202. Journal of clinical oncology. 2018;36(4):326–32. https://dx.doi.org/10.1200/JCO.2017.74.6651.
- Henry N.L., Unger J.M., Till C., et al. Association between body mass index and response to dulox-etine for aromatase inhibitor-associated musculoskeletal symptoms in SWOG S1202. Cancer. 2019;125(12):2123–9. https://dx.doi.org/10.1002/cncr.32024
- Pineda-Moncusí M., Garcia-Giralt N., Diez-Perez A., et al. Increased fracture risk in women treated with aromatase inhibitors versus tamoxifen: beneficial effect of bisphosphonates. J Bone Mineral Res. 2020;35(2):291–7. https://dx.doi.org/10.1002/jbmr.3886
- Santa-Maria C.A., Bardia A., Blackford A.L., et al. A phase II study evaluating the efficacy of zoledronic acid in prevention of aromatase inhibitor-associated musculoskeletal symptoms: the ZAP trial. Breast Cancer Res Treatment. 2018;171(1):121–9. https://dx.doi.org/10.1007/s10549-018-4811-1
- Alhanafy A.M., Labeeb A., Khalil A. The role of diuretics in treatment of aromatase inhibitors induced musculoskeletal symptoms in women with non metastatic breast cancer. Asian Pacific J Cancer Prevent. 2018;19(12):3525–31. https://dx.doi.org/10.31557/APJCP.2018.19.12.3525
- Hershman D.L., Unger J.M., Greenlee H., et al. Effect of Acupuncture vs Sham Acupuncture or Waitlist Control on Joint Pain Related to Aromatase Inhibitors Among Women With Early-Stage Breast Cancer: A Randomized Clinical Trial. JAMA. 2018;320(2):167–76. https://dx.doi.org/10.1001/jama.2018.11970
- Yu K., Portes P., Morris G.S., et al. The role of exercise in aromatase inhibitor-induced arthralgia. J Cancer Surviv. 2024;18(3):789–801. https://dx.doi.org/10.1007/s11764-024-01612-4
补充文件

