Skip to main content

Advertisement

SpringerLink
Log in

Musculoskeletal events associated with the management of endocrine-responsive breast cancer

  • Review
  • Published:
Oncology Reviews

Abstract

Musculoskeletal symptoms have been reported in patients treated with third generation aromatase inhibitors (AIs) and with blockers of hypothalamic–pituitary gonadal axis. AIs act by suppressing postmenopausal estrogen biosynthesis through inhibition of the enzyme aromatase, which is responsible for the conversion of androgens to estrogens in many tissues. Maximal estrogen and/or androgen deprivation is beneficial for cancer growth suppression but could be associated with side effects such as accelerated bone loss and osteoporotic fractures which are extensively reported. Musculoskeletal events, another group of adverse events, have been studied to a lesser extent and are usually commonly reported as arthralgia and myalgia. Furthermore, the pathogenesis and anatomical findings of musculoskeletal symptoms have not been adequately elucidated. In this communication, we review recent information related to musculoskeletal symptoms in breast cancer and speculate on possible explanations for musculoskeletal pain related to hormone deprivation. We outline treatment options for control of arthralgia and myalgia due to hormonal therapy. More knowledge about the etiology and management of musculoskeletal adverse effects breast cancer during endocrine therapy is needed because discontinuation of the treatment due to intolerant symptomatology may result in disruption of the treatment schedule.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Buzdar AU (2003) Pharmacology and pharmacokinetics of the newer generation aromatase inhibitors. Clin Cancer Res 9:468S–472S

    CAS  PubMed  Google Scholar 

  2. Buzdar A, Douma J, Davidson N et al (2001) Phase III, multicenter, double-blind, randomized study of letrozole, an aromatase inhibitor, for advanced breast cancer versus megestrol acetate. J Clin Oncol 19:3357–3366

    CAS  PubMed  Google Scholar 

  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 randomised controlled trial. Lancet 369:559–570

    Article  CAS  PubMed  Google Scholar 

  4. Briest S, Davidson NE (2007) Aromatase inhibitors for breast cancer. Rev Endocr Metab Disord 8:215–228

    Article  CAS  PubMed  Google Scholar 

  5. Coleman RE, Bolten WW, Lansdown M et al (2008) Aromatase inhibitor-induced arthralgia: clinical experience and treatment recommendations. Cancer Treat Rev 34:275–282

    Article  CAS  PubMed  Google Scholar 

  6. Buzdar A, Howell A, Cuzick J et al (2006) Comprehensive side-effect profile of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: long-term safety analysis of the ATAC trial. Lancet Oncol 7:633–643

    Article  CAS  PubMed  Google Scholar 

  7. Coates AS, Keshaviah A, Thurlimann 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 25:486–492

    Article  CAS  PubMed  Google Scholar 

  8. Boccardo F, Rubagotti A, Guglielmini P et al (2006) Switching to anastrozole versus continued tamoxifen treatment of early breast cancer. Updated results of the Italian tamoxifen anastrozole (ITA) trial. Ann Oncol 17(Suppl 7):vii10–vii14

    Article  PubMed  Google Scholar 

  9. Goss PE, Strasser K (2001) Aromatase inhibitors in the treatment and prevention of breast cancer. J Clin Oncol 19:881–894

    CAS  PubMed  Google Scholar 

  10. Mincey BA, Duh MS, Thomas SK et al (2006) Risk of cancer treatment-associated bone loss and fractures among women with breast cancer receiving aromatase inhibitors. Clin Breast Cancer 7:127–132

    Article  CAS  PubMed  Google Scholar 

  11. Crew KD, Greenlee H, Capodice J et al (2007) Prevalence of joint symptoms in postmenopausal women taking aromatase inhibitors for early-stage breast cancer. J Clin Oncol 25:3877–3883

    Article  PubMed  Google Scholar 

  12. Cleeland CS (1989) Measurement of pain by subjective report. In: Chapman CR, Loeser JD (eds) Issues in pain management, vol 12: Advances in pain research and therapy. Raven Press, New York, pp 391–403

  13. Dieppe PA, Lohmander LS (2005) Pathogenesis and management of pain in osteoarthritis. Lancet 365:965–973

    Article  CAS  PubMed  Google Scholar 

  14. Chlebowski RT (2009) Aromatase inhibitor-associated arthralgias. J Clin Oncol 27:4932–4934

    Article  PubMed  Google Scholar 

  15. Richette P, Corvol M, Bardin T (2003) Estrogens, cartilage, and osteoarthritis. Joint Bone Spine 70:257–262

    Article  PubMed  Google Scholar 

  16. Smith YR, Stohler CS, Nichols TE et al (2006) Pronociceptive and antinociceptive effects of estradiol through endogenous opioid neurotransmission in women. J Neurosci 26:5777–5785

    Article  CAS  PubMed  Google Scholar 

  17. Ushiyama T, Ueyama H, Inoue K et al (1999) Expression of genes for estrogen receptors alpha and beta in human articular chondrocytes. Osteoarthr Cartil 7:560–566

    Article  CAS  PubMed  Google Scholar 

  18. Claassen H, Hassenpflug J, Schunke M et al (2001) Immunohistochemical detection of estrogen receptor alpha in articular chondrocytes from cows, pigs and humans: in situ and in vitro results. Ann Anat 183:223–227

    Article  CAS  PubMed  Google Scholar 

  19. Le Bail J, Liagre B, Vergne P et al (2001) Aromatase in synovial cells from postmenopausal women. Steroids 66:749–757

    Article  CAS  PubMed  Google Scholar 

  20. Levine JD, Gordon NC, Jones RT et al (1978) The narcotic antagonist naloxone enhances clinical pain. Nature 272:826–827

    Article  CAS  PubMed  Google Scholar 

  21. 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 104:87–91

    Article  CAS  PubMed  Google Scholar 

  22. Loughlin J (2003) Genetics of osteoarthritis and potential for drug development. Curr Opin Pharmacol 3:295–299

    Article  CAS  PubMed  Google Scholar 

  23. Henry NL, Giles JT, Ang D et al (2008) Prospective characterization of musculoskeletal symptoms in early stage breast cancer patients treated with aromatase inhibitors. Breast Cancer Res Treat 111:365–372

    Article  CAS  PubMed  Google Scholar 

  24. Goss PE, Ingle JN, Martino S et al (2005) Randomized trial of letrozole following tamoxifen as extended adjuvant therapy in receptor-positive breast cancer: updated findings from NCIC CTG MA.17. J Natl Cancer Inst 97:1262–1271

    Article  CAS  PubMed  Google Scholar 

  25. Jakesz R, Jonat W, Gnant M et al (2005) Switching of postmenopausal women with endocrine-responsive early breast cancer to anastrozole after 2 years’ adjuvant tamoxifen: combined results of ABCSG trial 8 and ARNO 95 trial. Lancet 366:455–462

    Article  CAS  PubMed  Google Scholar 

  26. Boccardo F, Rubagotti A, Puntoni M et al (2005) Switching to anastrozole versus continued tamoxifen treatment of early breast cancer: preliminary results of the Italian Tamoxifen Anastrozole Trial. J Clin Oncol 23:5138–5147

    Article  CAS  PubMed  Google Scholar 

  27. Sestak I, Sapunar F, Cuzick J (2009) Aromatase inhibitor-induced carpal tunnel syndrome: results from the ATAC trial. J Clin Oncol 27:4961–4965

    Article  CAS  PubMed  Google Scholar 

  28. Loprinzi CL, Duffy J, Ingle JN (1993) Postchemotherapy rheumatism. J Clin Oncol 11:768–770

    CAS  PubMed  Google Scholar 

  29. Katz J, Savior DC, Gilman P et al (2010) Feasibility of an exercise program for aromatase inhibitor-related arthralgia (AIRA) in breast cancer survivors. J Clin Oncol, AScO annual meeting proceedings, 2010 TPS 101, 28 (#15S):75

  30. Crew KD, Capodice JL, Greenlee H et al (2010) Randomized, blinded, sham-controlled trial of acupuncture for the management of aromatase inhibitor-associated joint symptoms in women with early-stage breast cancer. J Clin Oncol 28:1154–1160

    Google Scholar 

  31. Holick MF (2007) Vitamin D deficiency. N Engl J Med 357:266–281

    Article  CAS  PubMed  Google Scholar 

  32. Plotnikoff GA, Quigley JM (2003) Prevalence of severe hypovitaminosis D in patients with persistent, nonspecific musculoskeletal pain. Mayo Clin Proc 78:1463–1470

    Article  PubMed  Google Scholar 

  33. Warner AE, Arnspiger SA (2008) Diffuse musculoskeletal pain is not associated with low vitamin D levels or improved by treatment with vitamin D. J Clin Rheumatol 14:12–16

    Article  PubMed  Google Scholar 

  34. Cecil RL, Archer BH (1925) Arthritis of the menopause. JAMA 84:75–79

    Google Scholar 

  35. Pansini F, Albertazzi P, Bonaccorsi G et al (1994) The menopausal transition: a dynamic approach to the pathogenesis of neurovegetative complaints. Eur J Obstet Gynecol Reprod Biol 57:103–109

    Article  CAS  PubMed  Google Scholar 

  36. Nevitt MC, Cummings SR, Lane NE et al (1996) Association of estrogen replacement therapy with the risk of osteoarthritis of the hip in elderly white women Study of Osteoporotic Fractures Research Group. Arch Intern Med 156:2073–2080

    Article  CAS  PubMed  Google Scholar 

  37. Haynes BP, Dowsett M, Miller WR et al (2003) The pharmacology of letrozole. J Steroid Biochem Mol Biol 87:35–45

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The valuable technical assistance of Mrs. Tammy Dohm is highly appreciated.

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Division of Hematology/Oncology, Department of Medicine, Michigan State University, B413 Clinical Center, 138 Service Road, East Lansing, MI, 48824, USA

    Anas Al-Janadi, Borys Hrinczenko, Vijay Chaudhary, Shalini Chitneni, Sarah Ali, Jennifer Saultz & Nikolay V. Dimitrov

Authors
  1. Anas Al-Janadi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Borys Hrinczenko
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Vijay Chaudhary
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shalini Chitneni
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sarah Ali
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jennifer Saultz
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Nikolay V. Dimitrov
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nikolay V. Dimitrov.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Al-Janadi, A., Hrinczenko, B., Chaudhary, V. et al. Musculoskeletal events associated with the management of endocrine-responsive breast cancer. Oncol Rev 4, 185–189 (2010). https://doi.org/10.1007/s12156-010-0057-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12156-010-0057-9

Keywords

Search

Navigation