J Korean Surg Soc.  2013 Nov;85(5):205-211.

Aromatase inhibitor-associated musculoskeletal symptoms: incidence and associated factors

• Park JY
• Lee SK
• Bae SY
• Kim J
• Kim MK
• Kil WH
• Lee JE
• Nam SJ

Abstract

PURPOSE
Arthralgia is the most common side effect in breast cancer patients receiving aromatase inhibitor (AI) therapy. Few studies have evaluated the risk factors, onset, and incidence of musculoskeletal pain in these patients. This study identifies the risk factors of AI-related severe arthralgia and their prevalence.
METHODS
All the clinical and pathological records of postmenopausal patients diagnosed with invasive breast cancer using AI at Samsung Medical Center from January 2005 to November 2007 were reviewed. Multivariate logistic regression analyses were performed to evaluate the risk factors of AI-associated musculoskeletal symptoms (AIMSS) and factors associated with AI discontinuance.
RESULTS
Among 299 patients, 69 patients (23%) experienced musculoskeletal symptoms attributed to AI use. In multivariate logistic regression analysis, no statistically significant outcome was found to confirm the risk factors for the development of AIMSS. Among the 69 patients who experienced AI-associated musculoskeletal symptoms, 29 (39.7%) discontinued AI use. Multivariate logistic regression analyses revealed an association of prior tamoxifen use with discontinuance of AI (P < 0.01; odds ratio, 4.27; 95% confidence interval, 1.74 to 10.50).
CONCLUSION
Prior use of tamoxifen is related to discontinuation of AI due to AI-associated severe arthralgia. Special monitoring and proper pain control for these patients should be considered during the treatment period.

Keyword

Aromatase inhibitors; Aromatase inhibitor-associated musculoskeletal symptoms; Prior tamoxifen

MeSH Terms

Aromatase Inhibitors
Aromatase*
Arthralgia
Breast Neoplasms
Humans
Incidence*
Logistic Models
Musculoskeletal Pain
Odds Ratio
Risk Factors
Tamoxifen
Aromatase
Aromatase Inhibitors
Tamoxifen

Reference

1. Sestak I, Cuzick J, Sapunar F, Eastell R, Forbes JF, Bianco AR, et al. Risk factors for joint symptoms in patients enrolled in the ATAC trial: a retrospective, exploratory analysis. Lancet Oncol. 2008; 9:866–872.

2. Crew KD, Greenlee H, Capodice J, Raptis G, Brafman L, Fuentes D, et al. Prevalence of joint symptoms in postmenopausal women taking aromatase inhibitors for early-stage breast cancer. J Clin Oncol. 2007; 25:3877–3883.

3. Din OS, Dodwell D, Wakefield RJ, Coleman RE. Aromatase inhibitor-induced arthralgia in early breast cancer: what do we know and how can we find out more? Breast Cancer Res Treat. 2010; 120:525–538.

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

5. Coates AS, Keshaviah A, Thurlimann B, Mouridsen H, Mauriac L, Forbes JF, et al. 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. 2007; 25:486–492.

6. Donnellan PP, Douglas SL, Cameron DA, Leonard RC. Aromatase inhibitors and arthralgia. J Clin Oncol. 2001; 19:2767.

7. Dent SF, Hopkins S, Di Valentin T, Verreault J, Vandermeer L, Verma S. Adjuvant aromatase inhibitors in early breast cancer-toxicity and adherence. Important observations in clinical practice. Breast Cancer Res Treat. 2007; 106:S111.

8. Henry NL, Giles JT, Ang D, Mohan M, Dadabhoy D, Robarge J, et al. Prospective characterization of musculoskeletal symptoms in early stage breast cancer patients treated with aromatase inhibitors. Breast Cancer Res Treat. 2008; 111:365–372.

9. Mao JJ, Stricker C, Bruner D, Xie S, Bowman MA, Farrar JT, et al. Patterns and risk factors associated with aromatase inhibitor-related arthralgia among breast cancer survivors. Cancer. 2009; 115:3631–3639.

10. Muslimani AA, Spiro TP, Chaudhry AA, Taylor HC, Jaiyesimi I, Daw HA. Aromatase inhibitor-related musculoskeletal symptoms: is preventing osteoporosis the key to eliminating these symptoms? Clin Breast Cancer. 2009; 9:34–38.

11. Mincey BA, Duh MS, Thomas SK, Moyneur E, Marynchencko M, Boyce SP, et al. Risk of cancer treatment-associated bone loss and fractures among women with breast cancer receiving aromatase inhibitors. Clin Breast Cancer. 2006; 7:127–132.

12. Confavreux CB, Fontana A, Guastalla JP, Munoz F, Brun J, Delmas PD. Estrogen-dependent increase in bone turnover and bone loss in postmenopausal women with breast cancer treated with anastrozole. Prevention with bisphosphonates. Bone. 2007; 41:346–352.