Breast Cancer Research and Treatment

, Volume 120, Issue 1, pp 127–134

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

  • Karine Briot
  • Michèle Tubiana-Hulin
  • Laurent Bastit
  • Ioana Kloos
  • Christian Roux
Clinical trial

Abstract

The objective of the present study was to evaluate the effect of the switch of aromatase inhibitors (AIs) on musculoskeletal symptoms in postmenopausal women with hormone-receptor-positive breast cancer. This was a 6-month, prospective, non-randomized, multicenter study. Patients who had discontinued anastrozole due to musculoskeletal symptoms were eligible to participate in this study, and received letrozole, which was initiated 1 month after anastrozole discontinuation. Musculoskeletal symptoms were systematically assessed for severity, location of the symptoms, presence of swelling and of morning stiffness by the oncologist patients when patients stopped taking their anastrozole, 1 month after the discontinuation of anastrozole, and 1, 3, and 6 months after initiating the letrozole therapy. The primary endpoint was the percentage of patients who discontinued letrozole due to the severe musculoskeletal symptoms. After switching from anastrozole therapy, and at the end of the 6-month letrozole treatment, 128 (71.5%) out of 179 patients (61.3 ± 8.4 years) continued with letrozole. Fifty-one patients (28.5%) discontinued treatment due to severe joint pain. At the end of the 6-month, 116 patients (73.9%) had arthralgia, 33 (21.0%) myalgia, 25 (15.9%) arthritis, 22 (14.0%) tendinitis, and 20 (12.7%) polyalgic syndrome. Bivariate analysis of the factors associated with letrozole discontinuation showed that the duration of a prior anastrozole treatment was a significant predictor (P = 0.04). This study shows that in patients intolerant to one AI, switching to another agent allows a higher proportion of patients to continue the therapy and maximize hormonal adjuvant therapy and disease outcome benefits.

Keywords

Aromatase inhibitors Letrozole Musculoskeletal symptoms Postmenopausal breast cancer 

References

  1. 1.
    Winer EP, Hudis C, Burstein HJ et al (2005) American Society of Clinical Oncology technology assessment on the use of aromatase inhibitors as adjuvant therapy for postmenopausal women with hormone receptor positive breast cancer: status report 2004. J Clin Oncol 23:619–629CrossRefPubMedGoogle Scholar
  2. 2.
    Howell A, Cuzick J, Baum M et al (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
  3. 3.
    Coombes RC, Kilburn LS, Snowdon CF et al (2007) Survival and safety of exemestane versus tamoxifen after 2–3 years’ tamoxifen treatment (Intergroup Exemestane Study): a randomized controlled trial. Lancet 369:559–570CrossRefPubMedGoogle Scholar
  4. 4.
    Coates AS, Keshaviah A, Thürlimann B et al (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
  5. 5.
    Poole R, Paridaens R (2007) The use of third generation aromatase inhibitors and tamoxifen in the adjuvant treatment of postmenopausal patients with hormone-dependent breast cancer: evidence based review. Curr Opin Oncol 19:564–572CrossRefPubMedGoogle Scholar
  6. 6.
    Morales L, Neven P, Paridaens R (2005) Choosing between an aromatase inhibitor and tamoxifen in the adjuvant setting. Curr Opin Oncol 17:559–565CrossRefPubMedGoogle Scholar
  7. 7.
    Dowsett M, Howell A (2002) Breast cancer: aromatase inhibitors take on tamoxifen. Nat Med 12:1341–1344CrossRefGoogle Scholar
  8. 8.
    Felson DT, Cummings SR (2005) Aromatase inhibitors and the syndrome of arthralgias with estrogen deprivation. Arthritis Rheum 52:2594–2598CrossRefPubMedGoogle Scholar
  9. 9.
    Donnellan P, Douglas S, Cameron D, Leonard RC (2001) Aromatase inhibitors and arthralgia. J Clin Oncol 19:2767PubMedGoogle Scholar
  10. 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. J Clin Oncol 25:3877–3883CrossRefPubMedGoogle Scholar
  11. 11.
    Morales L, Pans S, Verschueren K et al (2008) Prospective study to assess short-term intra-articular and tenosynovial changes in the aromatase inhibitor-associated arthralgia syndrome. J Clin Oncol 26:3147–3152CrossRefPubMedGoogle Scholar
  12. 12.
    Morales L, Pans S, Paridaens R et al (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
  13. 13.
    Coleman RE, Bolten WW, Lansdown M, Dale S, Jackisch C, Merkel D, Maass N, Hadji P (2008) Aromatase inhibitor-induced arthralgia: clinical experience and treatment recommendations. Cancer Treat Rev 34:275–282CrossRefPubMedGoogle Scholar
  14. 14.
    Partridge AH, LaFountain A, Mayer E, Taylor BS, Winer E, Asnis-Alibozek A (2008) Adherence to initial adjuvant anastrozole therapy among women with early-stage breast cancer. J Clin Oncol 26:556–562CrossRefPubMedGoogle Scholar
  15. 15.
    Renshaw L, McHugh M, Williams L et al (2007) Comparison of joint problems as reported by patients in a randomized adjuvant trial of anastrozole and letrozole. Breast Cancer Res Treat 106:S108Google Scholar
  16. 16.
    Cleeland CS (1989) Measurement of pain by subjective report. In: Chapman CR, Loeser JD (eds) Issues in pain measurement. Advances in pain research and therapy, vol 12. Raven Press, New York, pp 391–403Google Scholar
  17. 17.
    Roth SH, Fleischmann RM, Burch FX, Dietz F, Bockow B, Rapoport RJ, Rutstein J, Lacouture PG (2000) Around-the-clock, controlled-release oxycodone therapy for osteoarthritis-related pain: placebo-controlled trial and long-term evaluation. Arch Intern Med 160:853–860CrossRefPubMedGoogle Scholar
  18. 18.
    Ware J Jr, Kosinski M, Keller SD (1996) A 12-item short-form health survey: construction of scales and preliminary tests of reliability and validity. Med Care 34:220–233CrossRefPubMedGoogle Scholar
  19. 19.
    Guillemin F, Briançon S, Pourel J (1992) Validity and discriminant ability of the HAQ Functional Index in early rheumatoid arthritis. Disabil Rehabil 14:71–77CrossRefPubMedGoogle Scholar
  20. 20.
    Thomas R, Godward S, Makris A, Bloomfield D, Moody AM, Williams M (2004) Giving patients a choice improves quality of life: a multi-centre, investigator-blind, randomised, crossover study comparing letrozole with anastrozole. Clin Oncol (R Coll Radiol) 16:485–491Google Scholar
  21. 21.
    Croft P, Rigby AS, Boswell R, Schollum J, Silman A (1993) The prevalence of chronic widespread pain in the general population. J Rheumatol 20:710–713PubMedGoogle Scholar
  22. 22.
    Sestak I, Cuzick J, Sapunar F, Eastell R, Forbes JF, Bianco AR, Buzdar AU, ATAC Trialists’ Group (2008) Risk factors for joint symptoms in patients enrolled in the ATAC trial: a retrospective, exploratory analysis. Lancet Oncol 9:866–872CrossRefPubMedGoogle Scholar
  23. 23.
    Buzdar AU, The ATAC Trialists’ Group (2006) Clinical features of joint symptoms observed in the “Arimidex, Tamoxifen, alone or in combination (ATAC) trial”. J Clin Oncol 24:551CrossRefGoogle Scholar
  24. 24.
    Zumoff B (1982) Relationship of obesity to blood estrogens. Cancer Res 42(8 Suppl):289–294Google Scholar

Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  • Karine Briot
    • 1
  • Michèle Tubiana-Hulin
    • 2
  • Laurent Bastit
    • 3
  • Ioana Kloos
    • 4
  • Christian Roux
    • 1
  1. 1.Rheumatology Department, Cochin Hospital, Rheumatology DepartmentParis Descartes UniversityParisFrance
  2. 2.René Huguenin InstituteSt CloudFrance
  3. 3.Frédéric Joliot CenterRouenFrance
  4. 4.NovartisRueil MalmaisonFrance

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