Aromatase Inhibitor-associated Bone Loss in Breast Cancer

Aromatase Inhibitor-associated Bone Loss in Breast Cancer

Peyman Hadji
US Oncological Disease 2007 - Issue I
Published: October 2008
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In 2006, breast cancer was the most commonly diagnosed cancer among women, comprising approximately 31% of new cancer cases, and resulting in 15% of all cancer-related deaths in the US.1 In a large proportion of the newly diagnosed breast cancer cases, breast cancer tumors are hormone-responsive; therefore, estrogen and its receptor have become the targets of choice for therapeutic intervention. Estrogen suppression prevents or reduces growth of estrogen receptor-positive (ER+) tumors, and can be achieved through surgical or targeted therapeutic modalities. Early surgical and radiological ovarian ablation strategies have given way to more targeted therapies involving the detection of ER status and compounds such as tamoxifen that block tumor-cell growth at the ER level. Tamoxifen was the therapy of choice for hormone-responsive breast cancer and is still commonly prescribed. However, many patients still experience disease recurrence despite ongoing tamoxifen therapy. Furthermore, tamoxifen is associated with serious adverse events, most notably thromboembolism (blood clots) and endometrial cancer, and therapy is limited to five years. Therefore, alternative approaches with improved efficacy to target ER+ breast cancer tumors have been developed.

Aromatase inhibitors (AIs) block estrogen production in the peripheral tissues by preventing the last step in estrogen biosynthesis. The superior efficacy and more favorable side-effect profile demonstrated by AIs have allowed them to begin to replace tamoxifen as the adjuvant therapy of choice for post-menopausal women with ER+ breast cancer.2–5 However, one caveat of AI therapy is accelerated bone loss and increased fracture risk in a population of women that may already be at risk for fracture related to chemotherapy, low bone mineral density (BMD), age, history of fragility fracture after the age of 50, family history of hip fracture, or treatment history.4–8 The goal of adjuvant hormonal therapy for early breast cancer is to prevent local or distant disease recurrence or prolong disease-free survival (DFS) or overall survival (OS). Recent head-to-head clinical trials demonstrate that AI treatment is superior to tamoxifen for achieving this goal. To this end, maximum clinical benefit may be achieved by combining AI therapy with bisphosphonates in patients at risk for fracture to ensure optimal breast cancer management and prevent bone loss.9,10 This review briefly summarizes the available data regarding aromatase inhibitor-associated bone loss (AIBL) and provides insight into ongoing trials for the prevention of AIBL with bisphosphonates.

Bone Loss and Fracture Risk Associated with Breast Cancer
In general, women reach their peak BMD around age 20–30. The most significant loss occurs at menopause and subsequently slows to approximately 1% per year thereafter.11 Reduction in serum estrogen is directly responsible for bone loss and changes in the bone microarchitecture that lead to increased fracture risk. One large prospective study of women ≥65 years old demonstrated a direct association between estrogen levels and fracture incidence. Women in this study who had undetectable estrogen levels had an increased risk of hip and vertebral fractures compared with women who had very low but still detectable estrogen levels.12 Thus, chemotherapy and cancer treatment regimens that either directly or indirectly reduce circulating estrogen can have a dramatic deleterious effect on bone and fracture risk.

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References:

 

  1. Jemal A, et al., CA Cancer J Clin, 2006;56:106–30.
  2. Buzdar AU, Breast Dis, 2005;24:107–17.
  3. Coates AS, et al., J Clin Oncol, 2007;25:486–92.
  4. Coombes RC, et al., Lancet, 2007;369:559–70.
  5. Howell A, et al., Lancet, 2005;365:60–62.
  6. Goss PE, et al., J Natl Cancer Inst, 2005;97:1262–71.
  7. Jakesz R, et al., Lancet, 2005;366:455–62.
  8. Thurlimann B, et al., N Engl J Med, 2005;353:2747–57.
  9. Brufsky A, et al., J Clin Oncol, 2007;25:829–36.
  10. Gnant MF, et al., J Clin Oncol, 2007;25:820–28.
  11. Osteoporos Int, 1997;7:1–6.
  12. Cummings SR, et al., N Engl J Med, 1998;339:733–8.
  13. Kanis JA, Br J Cancer, 1999;79:1179–81.
  14. Chen Z, et al., Arch Intern Med, 2005;165:552–8.
  15. Shapiro CL, et al., J Clin Oncol, 2001;19:3306–11.
  16. Vehmanen L, et al., J Clin Oncol, 2006;24:675–80.
  17. Whannel K, et al., Breast Cancer Res Treat, 2006;100:S187 (Abstract 4046).
  18. Geisler J, et al., J Clin Oncol, 2002;20:751–7.
  19. Geisler J, et al., Clin Cancer Res, 1998;4:2089–93.
  20. Goss PE, et al., J Clin Oncol, 2007;25:2006–11.
  21. Coleman RE, Lancet Oncol, 2007;8:119–27.
  22. Eastell R, et al., J Bone Miner Res, 2006;21:1215–23.
  23. Coleman R, J Clin Oncol, 2006;24 Suppl:5s. (Abstract 511).
  24. Siris ES, et al., Arch Intern Med, 2004;164:1108–12.
  25. Hillner BE, et al., J Clin Oncol, 2003;21:4042–57.
  26. National Osteoporosis Foundation, Physicians Guide: Pharmacologic Options, available at: www.nof.org/physguide/phamacologic.htm. Accessed March 8, 2007.
  27. World Health Organization, Prevention and Management of Osteoporosis, WHO Technical Report Series 921, 2003;1–192.
  28. Aapro M, Breast, 2006;15(Suppl. 1):S30-40.
  29. Brufsky A, et al., Breast Cancer Res Treat, 2006;100(Suppl. 1):S25 (Abstract 107).
  30. Brufsky A, et al., Breast Cancer Res Treat, 2006;100(Suppl. 1):S233 (Abstract 5060).
  31. Saarto T, et al., Br J Cancer, 1997;75:602–5.
  32. Delmas PD, et al., J Clin Oncol, 1997;15:955–62.
  33. Saarto T, et al., J Clin Oncol, 2006;24(Suppl.):46S (Abstract 676).
  34. Siris ES, et al., Mayo Clin Proc, 2006;81:1013–22.
  35. Coombes RC, et al., N Engl J Med, 2004;350:1081–92.



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