Article

Etiology, Assessment, and Management of Aromatase Inhibitor-Related Musculoskeletal Symptoms

So-Hyun Park

M. Tish Knobf

Karen M. Sutton

aromatase inhibitors, Assessment
CJON 2012, 16(3), 260-266. DOI: 10.1188/12.CJON.260-266

Aromatase inhibitors (AIs) are recommended as adjuvant endocrine therapy for postmenopausal women with hormone-responsive breast cancer. With the widespread use of AI adjuvant endocrine therapy, a significant profile of musculoskeletal symptoms has emerged. Moderate to severe musculoskeletal symptoms have led some women to discontinue therapy, compromising the survival benefit. The etiology of AI-related musculoskeletal symptoms is poorly understood, which challenges development of effective management strategies. The purpose of this article is to describe AI-related musculoskeletal symptoms, review possible causes, provide assessment guidelines, and recommend management strategies based on the best available evidence. Little evidence exists for effective management strategies of AI-related musculoskeletal symptoms, and randomized clinical trials are needed to establish effective interventions. A thorough musculoskeletal assessment can help guide clinical decision making for the best individual management approach. Providers need to manage symptoms with the best available evidence to minimize symptom distress and maximize adherence to AI therapy.

Jump to a section

    References

    Briot, K., Tubiana-Hulin, M., Bastit, L., Kloos, I., & Roux, C. (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 Research and Treatment, 120, 127-134.
    Burstein, H. J., Prestrud, A. A., Seidenfeld, J., Anderson, H., Bulchholz, T. A., Davidson, N. E.… Griggs, J. J. (2010). American Society of Clinical Oncology clinical practice guideline: Update on adjuvant endocrine therapy for women with hormone receptor-positive breast cancer. Journal of Clinical Oncology, 28, 3748-3796.
    Christensen, B. V., Iuhl, I. U., Vilbek, H., Bulow, H. H., Dreijer, N. C., & Rasmussen, H. F. (1992). Acupuncture treatment of severe knee osteoarthrosis. A long-term study. Acta Anaesthesiologica Scandinavica, 36, 519-525. doi:10.1111/j.1399-6576.1992.tb03511.x
    Crew, K. D., Capodice, J. L., Greenlee, H., Apollo, A., Jacobson, J. S., Raptis, G., … Hershman, D. L. (2007). Pilot study of acupuncture for the treatment of joint symptoms related to adjuvant aromatase inhibitor therapy in postmenopausal breast cancer patients. Journal of Cancer Survivorship, 1, 283-291.
    Crew, K. D., Capodice, J. L., Greenlee, H., Brafman, L., Fuentes, D., Awad, D., … Hershman, D. L. (2010). Randomized, blinded, sham-controlled trial of acupuncture for the management of aromatase inhibitor-associated joint symptoms in women with early-stage breast cancer. Journal of Clinical Oncology, 28, 1154-1160.
    Crew, K. D., Greenlee, H., Capodice, J., Raptis, G., Brafman, L., Fuentes, D., … Hershman, D. L. (2007). Prevalence of joint symptoms in postmenopausal women taking aromatase inhibitors for early-stage breast cancer. Journal of Clinical Oncology, 25, 3877-3883.
    Dent, S. F., Gaspo, R., Kissner, M., & Pritchard, K. I. (2011). Aromatase inhibitor therapy: Toxicities and management strategies in the treatment of postmenopausal women with hormone-sensitive early breast cancer. Breast Cancer Research Treatment, 126, 295-310. doi:10.1007/s10549-011-1351-3
    Dietrich, W., Haitel, A., Holzer, G., Huber, J. C., Kolbus, A., & Tschugguel, W. (2006). Estrogen receptor-beta is the predominant estrogen receptor subtype in normal human synovia. Journal of the Society for Gynecologic Investigation, 13, 512-517.
    Din, O. S., Dodwell, D., Wakefield, R. J., & Coleman, R. E. (2010). Aromatase inhibitor-induced arthralgia in early breast cancer: What do we know and how can we find out more? Breast Cancer Research and Treatment, 120, 525-538.
    Dizdar, O., Ozcakar, L., Malas, F. U., Harputluoglu, H., Bulut, N., Aksoy, S., … Altundag, K. (2009). Sonographic and electrodiagnostic evaluations in patients with aromatase inhibitor-related arthralgia. Journal of Clinical Oncology, 27, 4955-4960.
    Dowsett, M., Cuzick, J., Ingle, J., Coates, A., Forbes, J., Bliss, J., … Peto, R. (2010). Meta-analysis of breast cancer outcomes in adjuvant trials of aromatase inhibitors versus tamoxifen. Journal of Clinical Oncology, 28, 509-518. doi:10.1200/JCO.2009.23.1274
    Ernst, E., Lee, M., & Choi, T. (2011). Acupuncture: Does it alleviate pain and are there serious risks? A review of reviews. Pain, 152, 755-764. doi:10.1016/j.pain.2010.11.004
    Ezzo, J., Hadhazy, V., Birch, S., Lao, L., Kaplan, G., Hochberg, M., & Berman, B. (2001). Acupuncture for osteoarthritis of the knee: A systematic review. Arthritis and Rheumatism, 44, 819-825. doi:10.1002/1529-0131(200104)44:4<819::AID-ANR138>3.0.CO;2-P
    Fernihough, J. K., Richmond, R. S., Carlson, C. S., Cherpes, T., Holly, J. M., & Loeser, R. F. (1999). Estrogen replacement therapy modulation of the insulin-like growth factor system in monkey knee joints. Arthritis and Rheumatism, 42, 2103-2111.
    Freedman, R. A., & Winer, E. P. (2010). Adjuvant therapy for postmenopausal women with endocrine-sensitive breast cancer. Breast, 19, 69-75. doi:10.1016/j.breast.2009.11.009
    Guise, T. A., Brufsky, A., & Coleman, R. E. (2010). Understanding and optimizing bone health in breast cancer. Current Medical Research and Opinion, 26(Suppl. 3), 3-20.
    Hall, H. (2011). Acupuncture claims punctured: Not proven effective for pain, not harmless. Pain, 152, 711-712.
    Henry, N. L., Azzouz, F., Desta, Z., Li, L., Nguyen, A. T., Lemler, S., … Storniolo, A. M. (2012). Predictors of aromatase inhibitor discontinuation as a result of treatment-emergent symptoms in early stage breast cancer. Journal of Clinical Oncology, 30, 936-942.
    Henry, N. L., Giles, J. T., Ang, D., Mohan, M., Dadabhoy, D., Robarge, J., … Clauw, D. J. (2008). Prospective characterization of musculoskeletal symptoms in early stage breast cancer patients treated with aromatase inhibitors. Breast Cancer Research and Treatment, 111, 365-372. doi:10.1007/s10549-007-9774-6
    Henry, N. L., & Stearns, V. (2010). One size does not fit all: Quality of life during adjuvant aromatase inhibitor therapy. Breast Cancer Research and Treatment, 125, 751-753.
    Ingle, J. N., Schaid, D. J., Goss, P. E., Liu, M., Mushiroda, T., Chapman, J. A., … Weinshilboum, R. M. (2010). Genome-wide associations and functional genomic studies of musculoskeletal adverse events in women receiving aromatase inhibitors. Journal of Clinical Oncology, 28, 4674-4682. doi:10.1200/JCO.2010.28.5064
    Jones, S. E., Cantrell, J., Vukelja, S., Pippen, J., O'Shaughnessy, J., Blum, J. L., … Asmar, L. (2007). Comparison of menopausal symptoms during the first year of adjuvant therapy with either exemestane or tamoxifen in early breast cancer: Report of a Tamoxifen Exemestane Adjuvant Multicenter trial substudy. Journal of Clinical Oncology, 25, 4765-4771. doi:10.1200/JCO.2007.10.8274
    Josefsson, M. L., & Leinster, S. J. (2010). Aromatase inhibitors versus tamoxifen as adjuvant hormonal therapy for estrogen sensitive early breast cancer in post-menopausal women: Meta-analyses of monotherapy, sequenced therapy, and extended therapy. Breast, 19, 76-83. doi:10.1016/j.breast.2009.12.010
    Khan, Q. J., Reddy, P. S., Kimler, B. F., Sharma, P., Baxa, S. E., O'Dea, A. P., … Fabian, C. J. (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 Research and Treatment, 119, 111-118. doi:10.1007/s10549-009-0495-x
    Mao, J. J., Stricker, C., Bruner, D., Xie, S., Bowman, M. A., Farrar, J. T., … DeMichele, A. (2009). Patterns and risk factors associated with aromatase inhibitor-related arthralgia among breast cancer survivors. Cancer, 115, 3631-3639. doi:10.1002/cncr.24419
    Miaskowski, C., Shockney, L., & Chlebowski, R. T. (2008). Adherence to oral endocrine therapy for breast cancer: A nursing perspective. Clinical Journal of Oncology Nursing, 12, 213-221.
    Millar, A. (2009). Exercise prescription for people with arthritis. In American College of Sports Medicine (Ed.), ACSM's resources manual for guidelines for exercise testing and prescription (6th ed., pp. 661-665). Philadelphia, PA: Lippincott Williams and Wilkins.
    Morales, L., Pans, S., Paridaens, R., Westhovens, R., Timmerman, D., … Neven, P. (2007). Debilitating musculoskeletal pain and stiffness with letrozole and exemestane: Associated tenosynovial changes on magnetic resonance imaging. Breast Cancer Researchand Treatment, 104, 87-91. doi:10.1007/s10549-006-9394-6
    Morales, L., Pans, S., Verschueren, K., Van Calster, B., Paridaens, R., Westhovens, R., … Neven, P. (2008). Prospective study to assess short-term intra-articular and tenosynovial changes in the aromatase inhibitor-associated arthralgia syndrome. Journal of Clinical Oncology, 26, 3147-3152. doi:10.1200/JCO.2007.15.4005
    Offit, K., & Robson, M. E. (2010). New pharmacogenomic paradigm in breast cancer treatment. Journal of Clinical Oncology, 28, 4665-4666. doi:10.1200/JCO.2010.31.2926
    Presant, C. A., Bosserman, L., Young, T., Vakil, M., Horns, R., Upadhyaya, G., … Howard, F. (2007). Aromatase inhibitor-associated arthralgia and/or bone pain: Frequency and characterization in nonclinical trial patients. Clinical Breast Cancer, 7, 775-778.
    Prieto-Alhambra, D., Javaid, M. K., Servitja, S., Arden, N. K., Martinez-Garcia, M., Diez-Perez, A., … Nogues, X. (2011). Vitamin D threshold to prevent aromatase inhibitor-induced arthralgia: A prospective cohort study. Breast Cancer Research and Treatment, 125, 869-878. doi:10.1007/s10549-010-1075-9
    Sugamata, N., Koibuchi, Y., Iino, Y., & Morishita, Y. (1999). A novel aromatase inhibitor, vorozole, shows antitumor activity and a decrease of tissue insulin-like growth factor-I level in 7, 12-dimethylbenz[a]anthracene-induced rat mammary tumors. International Journal of Oncology, 14, 259-263.
    Takeda, W., & Wessel, J. (1994). Acupuncture for the treatment of pain of osteoarthritic knees. Arthritis Care and Research, 7, 118-122. doi:10.1002/art.1790070304
    Vanderschueren, D., van Herck, E., Nijs, J., Ederveen, A. G., De Coster, R., & Bouillon, R. (1997). Aromatase inhibition impairs skeletal modeling and decreases bone mineral density in growing male rats. Endocrinology, 138, 2301-2307.
    Waltman, N. L., Ott, C. D., Twiss, J. J., Gross, G. J., & Lindsey, A. M. (2009). Vitamin D insufficiency and musculoskeletal symptoms in breast cancer survivors on aromatase inhibitor therapy. Cancer Nursing, 32, 143-150. doi:10.1097/01.NCC.0000339262.44560.92
    Zhang, Y., McAlindon, T. E., Hannan, M. T., Chaisson, C. E., Klein, R., Wilson, P. W., & Felson, D. T. (1998). Estrogen replacement therapy and worsening of radiographic knee osteoarthritis: The Framingham study. Arthritis and Rheumatism, 41, 1867-1873.