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Musculoskeletal Adverse Events Associated with Adjuvant Aromatase Inhibitors

By Qamar J. Khan, Anne P. O'Dea and Priyanka Sharma

Abstract

Musculoskeletal symptoms including arthralgia and myalgia occur frequently in aging women, particularly during the transition to menopause, when plasma estrogens precipitously decline. In postmenopausal women (PMW) with breast cancer, third-generation aromatase inhibitors (AIs) as adjuvant hormonal therapy have proven to be more effective, and to have a more predictable side effect profile, than tamoxifen. However, AIs further reduce plasma estrogens in PMW, exacerbating musculoskeletal symptoms. Clinical trial data have shown significantly higher incidences of arthralgia and myalgia with AIs compared with women on tamoxifen or placebo. Symptoms may be severe enough to significantly affect quality of life; musculoskeletal symptoms are a frequent reason for discontinuing therapy. In many cases, symptoms can be effectively managed with oral analgesics or other strategies. Early recognition and effective management of musculoskeletal symptoms can help maximize treatment compliance, enabling patients to derive optimal benefit from therapy in terms of preventing recurrence

Topics: Review Article
Publisher: Hindawi Publishing Corporation
OAI identifier: oai:pubmedcentral.nih.gov:2943085
Provided by: PubMed Central

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Citations

  1. (2007). A .S .C o a t e s ,A .K e s h a v i a h ,B .T h¨ urlimann 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
  2. (2005). A comparison of letrozole and tamoxifen in postmenopausal women withearlybreastcancer,”TheNewEnglandJournalofMedicine,
  3. (2007). Adjuvant aromatase inhibitors in breast cancer therapy: significance of musculoskeletal complications,”
  4. (2007). Aromatase inhibitor-associated arthralgia and/or bone pain: frequency and characterization in non-clinical trial patients,”
  5. (2007). Aromatase inhibitor-associated arthralgia syndrome,”
  6. (2006). Aromatase inhibitors: side effects reported by 622 women,”
  7. (2006). Bone safety of aromatase inhibitors versus tamoxifen,”
  8. (2007). Capodice et al., “Prevalence of joint symptoms in postmenopausal women taking aromatase inhibitors for early-stage breast cancer,”
  9. (2006). Clinical features of joint symptoms observed in the ‘Arimidex’, Tamoxifen, alone or in combination (ATAC)
  10. (2007). Comparison of joint problems reported by patients in a randomized adjuvant trial of anastrozole and letrozole,”
  11. (2007). Comparison of menopausal symptoms during the first year of adjuvant therapy with either exemestane or tamoxifen in early breast cancer:reportofatamoxifenexemestaneadjuvantmulticenter trial substudy,”
  12. (2002). Complementary therapies for reducing the risk of osteoporosis in patients receiving luteinizing hormonereleasinghormonetreatment/orchiectomyforprostatecancer: a review and assessment of the need for more research,”
  13. (2001). D o n n e l l a n ,S .L .D o u g l a s ,D .A .C a m e r o n ,a n dR
  14. (2007). Debilitating musculoskeletal pain and stiffness with letrozole and exemestane: associated tenosynovial changes on magnetic resonance imaging,”
  15. (1996). Diffusion of aromatase inhibitors for breast cancer therapy between
  16. (2010). Effect of a switch of aromatase inhibitors on musculoskeletal symptoms in postmenopausal women with hormonereceptor-positive breast cancer: the ATOLL (articular tolerance of letrozole) study,”
  17. (1989). Effects of estrogen oncirculating’free’andtotal1,25-dihydroxyvitaminDandon the parathyroid-vitamin D axis in postmenopausal women,”8
  18. (2004). Epidemiology, co-morbidity, and impact on health-related quality of life of self-reported headache and musculoskeletal pain—a gender perspective,”
  19. (2008). F o r b e s ,J .C u z i c k ,A .B u z d a r ,e ta l . ,“ E ffe c to fa n a s t r o z o l e and tamoxifen as adjuvant treatment for early-stage breast cancer: 100-month analysis of the ATAC trial,” The Lancet Oncology,
  20. (2009). Feasibility trial of electroacupuncture for aromatase inhibitor-related arthralgia in breast cancer survivors,” Integrative Cancer Therapies,
  21. FPIN’s clinical inquiries. Glucosamine and chondroitin for osteoarthritis,” AmericanFamilyPhysician,vol.73,no.7,pp.1245–1246,2006.
  22. (1986). G r e e r ,a n dL .M .D e m e r s ,“ T h ee ffect of endogenous estrogen fluctuation on metabolism of 25-hydroxyvitamin D,”
  23. (2007). Improved overall survival in postmenopausal women with early breast cancer after anastrozole initiated after treatment with tamoxifen compared with continued tamoxifen:
  24. (2005). Ingle et al., “Assessment of quality of life in MA. 17: a randomized, placebo-controlled trial of letrozole after 5 years of tamoxifen in postmenopausal women,”JournalofClinicalOncology,vol.23,no.28,pp.6931– 6940,
  25. (2010). K h a n ,P .S .R e d d y ,B .F .K i m l e re ta l . ,“ E ffect of vitamin D supplementation on serum 25-hydroxy vitamin D levels, joint pain, and fatigue in women starting adjuvant letrozole treatment for breast cancer,”
  26. (2009). Letrozole therapy alone or in sequence with tamoxifen in women with breast cancer,”
  27. (2004). Managing joint pain in primary care,”
  28. (2003). Meta-analysis of vascular and neoplastic events associated with tamoxifen,”
  29. Natural history of menopause symptoms in primary care patients: a MetroNet study,”
  30. (2003). Prevalence of severe hypovitaminosis D in patients with persistent, nonspecific musculoskeletalpain,”MayoClinicProceedings,vol.78,no.12,
  31. (2008). Prospective study to assess short-term intra-articular and tenosynovial changes in the aromatase inhibitor-associated arthralgia syndrome,”
  32. (2003). Quality of life and menopausal transition for middle-aged women on Kinmen island,”
  33. (2006). Quality of life in the intergroup exemestane study: a randomized trial of exemestane versus continued tamoxifen after 2 to 3 years of tamoxifen in postmenopausal women with primary breast cancer,”
  34. (2004). Quality of life of postmenopausal women in the Arimidex Tamoxifen, Alone or in Combination (ATAC) adjuvant breast cancer trial,”
  35. (2005). Randomized trial of letrozole following tamoxifen as extended adjuvant therapy in receptor-positive breast cancer: updated findings from
  36. (2008). Recognition and management of treatment-related side effects for breast cancer patients receiving adjuvant endocrine therapy,”
  37. (2005). Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years’ adjuvant treatment for breast cancer,”
  38. (2009). Results of the first planned analysis of the TEAM (tamoxifen exemestane adjuvant multinational) prospective randomized phase III trial in hormone sensitive postmenopausal early breast cancer,”
  39. (2008). Risk factors for joint symptoms in patients enrolled in the ATAC trial: a retrospective, exploratory analysis,”
  40. (1993). Sex steroids induced up-regulation of 1,25-(OH)2 vitamin D3 receptors in T 47D breast cancer cells,”
  41. (2006). Side effects of aromatase inhibitors versus tamoxifen: the patients’ perspective,”
  42. (2005). Smirnoff,a n dB . Schwartz, “Regulation of vitamin D receptor expression via estrogen-induced activation of the ERK 1/2 signaling pathway in colon and breast cancer cells,”
  43. (2009). Sonographic and electrodiagnostic evaluations in patients with aromatase inhibitor-related arthralgia,”
  44. (2007). Survival and safety of exemestane versus tamoxifen after 2-3 years’ tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial,”
  45. (2005). Switching of postmenopausal women with endocrine-responsive early breast cancer to anastrozole after 2 years’ adjuvant tamoxifen: combined results
  46. (2006). Tamoxifen, Alone or in Combination Trialists’ Group. Comprehensive side-effect profile of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: long-term safety analysis of
  47. (2008). Treatmentemergent endocrine symptoms and the risk of breast cancer recurrence: a retrospective analysis of
  48. (2006). W h e l a n ,K .I .P r i t c h a r d ,C .A r t e a g a ,S .C o m e ,a n dJ .I n g l e , “Managing patients on endocrine therapy: focus on qualityof-life issues,”