Kosin Med J.  2024 Jun;39(2):83-88. 10.7180/kmj.24.121.

Bone-modifying agents for bone metastasis in patients with breast cancer

Affiliations
  • 1Department of Internal Medicine, Pohang St. Mary's Hospital, Pohang, Korea
  • 2Department of Internal Medicine, Kosin University Gospel Hospital, Kosin University College of Medicine, Busan, Korea

Abstract

The bone is the most common location of breast cancer metastasis. Bone metastasis causes pain and skeletal-related events (SREs), and affects the quality of life and survival of breast cancer patients. Bone-modifying agents, including bisphosphonates and denosumab, reduce the risk of SREs in these patients. Among bisphosphonates, zoledronic acid is preferred due to its higher efficacy. Denosumab is marginally more effective than zoledronic acid in reducing the frequency of SREs. Patients with renal impairment should receive zoledronic acid with caution due to nephrotoxicity, and denosumab is an alternative option in these patients. Osteonecrosis of the jaw is a rare but severe complication of both zoledronic acid and denosumab, and all patients should undergo dental examinations before and during treatment. Although these drugs can reduce the risk of SREs in bone metastasis, no significant improvement in survival has been noted. This study reviews the effects and adverse events of bone-modifying agents for the treatment of bone metastasis from breast cancer.

Keyword

Bisphosphonate; Bone metastasis; Breast cancer; Denosumab

Reference

References

1. Liang Y, Zhang H, Song X, Yang Q. Metastatic heterogeneity of breast cancer: molecular mechanism and potential therapeutic targets. Semin Cancer Biol. 2020; 60:14–27.
2. Xiong Z, Deng G, Huang X, Li X, Xie X, Wang J, et al. Bone metastasis pattern in initial metastatic breast cancer: a population-based study. Cancer Manag Res. 2018; 10:287–95.
3. Gainford MC, Dranitsaris G, Clemons M. Recent developments in bisphosphonates for patients with metastatic breast cancer. BMJ. 2005; 330:769–73.
4. Yong M, Jensen AO, Jacobsen JB, Norgaard M, Fryzek JP, Sorensen HT. Survival in breast cancer patients with bone metastases and skeletal-related events: a population-based cohort study in Denmark (1999-2007). Breast Cancer Res Treat. 2011; 129:495–503.
5. Tahara RK, Brewer TM, Theriault RL, Ueno NT. Bone metastasis of breast cancer. Adv Exp Med Biol. 2019; 1152:105–29.
6. Ng TL, Tu MM, Ibrahim MF, Basulaiman B, McGee SF, Srikanthan A, et al. Long-term impact of bone-modifying agents for the treatment of bone metastases: a systematic review. Support Care Cancer. 2021; 29:925–43.
7. Wu X, Li F, Dang L, Liang C, Lu A, Zhang G. RANKL/RANK system-based mechanism for breast cancer bone metastasis and related therapeutic strategies. Front Cell Dev Biol. 2020; 8:76.
8. Venetis K, Piciotti R, Sajjadi E, Invernizzi M, Morganti S, Criscitiello C, et al. Breast cancer with bone metastasis: molecular insights and clinical management. Cells. 2021; 10:1377.
9. Roodman GD. Mechanisms of bone metastasis. N Engl J Med. 2004; 350:1655–64.
10. Goldvaser H, Amir E. Role of bisphosphonates in breast cancer therapy. Curr Treat Options Oncol. 2019; 20:26.
11. Drake MT, Clarke BL, Khosla S. Bisphosphonates: mechanism of action and role in clinical practice. Mayo Clin Proc. 2008; 83:1032–45.
12. O'Carrigan B, Wong MH, Willson ML, Stockler MR, Pavlakis N, Goodwin A. Bisphosphonates and other bone agents for breast cancer. Cochrane Database Syst Rev. 2017; 10:CD003474.
13. Palmieri C, Fullarton JR, Brown J. Comparative efficacy of bisphosphonates in metastatic breast and prostate cancer and multiple myeloma: a mixed-treatment meta-analysis. Clin Cancer Res. 2013; 19:6863–72.
14. Barrett-Lee P, Casbard A, Abraham J, Hood K, Coleman R, Simmonds P, et al. Oral ibandronic acid versus intravenous zoledronic acid in treatment of bone metastases from breast cancer: a randomised, open label, non-inferiority phase 3 trial. Lancet Oncol. 2014; 15:114–22.
15. Rosen LS, Gordon D, Kaminski M, Howell A, Belch A, Mackey J, et al. Zoledronic acid versus pamidronate in the treatment of skeletal metastases in patients with breast cancer or osteolytic lesions of multiple myeloma: a phase III, double-blind, comparative trial. Cancer J. 2001; 7:377–87.
16. Rosen LS, Gordon D, Kaminski M, Howell A, Belch A, Mackey J, et al. Long-term efficacy and safety of zoledronic acid compared with pamidronate disodium in the treatment of skeletal complications in patients with advanced multiple myeloma or breast carcinoma: a randomized, double-blind, multicenter, comparative trial. Cancer. 2003; 98:1735–44.
17. Park JH, Lee NK, Lee SY. Current understanding of RANK signaling in osteoclast differentiation and maturation. Mol Cells. 2017; 40:706–13.
18. Kiesel L, Kohl A. Role of the RANK/RANKL pathway in breast cancer. Maturitas. 2016; 86:10–6.
19. Stopeck AT, Lipton A, Body JJ, Steger GG, Tonkin K, de Boer RH, et al. Denosumab compared with zoledronic acid for the treatment of bone metastases in patients with advanced breast cancer: a randomized, double-blind study. J Clin Oncol. 2010; 28:5132–9.
20. Henry DH, Costa L, Goldwasser F, Hirsh V, Hungria V, Prausova J, et al. Randomized, double-blind study of denosumab versus zoledronic acid in the treatment of bone metastases in patients with advanced cancer (excluding breast and prostate cancer) or multiple myeloma. J Clin Oncol. 2011; 29:1125–32.
21. Lipton A, Fizazi K, Stopeck AT, Henry DH, Brown JE, Yardley DA, et al. Superiority of denosumab to zoledronic acid for prevention of skeletal-related events: a combined analysis of 3 pivotal, randomised, phase 3 trials. Eur J Cancer. 2012; 48:3082–92.
22. Henry D, Vadhan-Raj S, Hirsh V, von Moos R, Hungria V, Costa L, et al. Delaying skeletal-related events in a randomized phase 3 study of denosumab versus zoledronic acid in patients with advanced cancer: an analysis of data from patients with solid tumors. Support Care Cancer. 2014; 22:679–87.
23. Wang X, Yang KH, Wanyan P, Tian JH. Comparison of the efficacy and safety of denosumab versus bisphosphonates in breast cancer and bone metastases treatment: a meta-analysis of randomized controlled trials. Oncol Lett. 2014; 7:1997–2002.
24. Amadori D, Aglietta M, Alessi B, Gianni L, Ibrahim T, Farina G, et al. Efficacy and safety of 12-weekly versus 4-weekly zoledronic acid for prolonged treatment of patients with bone metastases from breast cancer (ZOOM): a phase 3, open-label, randomised, non-inferiority trial. Lancet Oncol. 2013; 14:663–70.
25. Hortobagyi GN, Van Poznak C, Harker WG, Gradishar WJ, Chew H, Dakhil SR, et al. Continued treatment effect of zoledronic acid dosing every 12 vs 4 weeks in women with breast cancer metastatic to bone: the OPTIMIZE-2 randomized clinical trial. JAMA Oncol. 2017; 3:906–12.
26. Himelstein AL, Foster JC, Khatcheressian JL, Roberts JD, Seisler DK, Novotny PJ, et al. Effect of longer-interval vs standard dosing of zoledronic acid on skeletal events in patients with bone metastases: a randomized clinical trial. JAMA. 2017; 317:48–58.
27. Awan AA, Hutton B, Hilton J, Mazzarello S, Van Poznak C, Vandermeer L, et al. De-escalation of bone-modifying agents in patients with bone metastases from breast cancer: a systematic review and meta-analysis. Breast Cancer Res Treat. 2019; 176:507–17.
28. Jensen AO, Jacobsen JB, Norgaard M, Yong M, Fryzek JP, Sorensen HT. Incidence of bone metastases and skeletal-related events in breast cancer patients: a population-based cohort study in Denmark. BMC Cancer. 2011; 11:29.
29. Alzahrani M, Stober C, Liu M, Awan A, Ng TL, Pond G, et al. Symptomatic skeletal-related events in patients receiving longer term bone-modifying agents for bone metastases from breast and castration resistant prostate cancers. Support Care Cancer. 2022; 30:3977–84.
30. Coleman R, Hadji P, Body JJ, Santini D, Chow E, Terpos E, et al. Bone health in cancer: ESMO Clinical Practice Guidelines. Ann Oncol. 2020; 31:1650–63.
31. Domschke C, Schuetz F. Side effects of bone-targeted therapies in advanced breast cancer. Breast Care (Basel). 2014; 9:332–6.
32. Body JJ, Bone HG, de Boer RH, Stopeck A, Van Poznak C, Damiao R, et al. Hypocalcaemia in patients with metastatic bone disease treated with denosumab. Eur J Cancer. 2015; 51:1812–21.
33. Tanvetyanon T, Stiff PJ. Management of the adverse effects associated with intravenous bisphosphonates. Ann Oncol. 2006; 17:897–907.
34. Perazella MA, Markowitz GS. Bisphosphonate nephrotoxicity. Kidney Int. 2008; 74:1385–93.
35. Allen MR, Burr DB. The pathogenesis of bisphosphonate-related osteonecrosis of the jaw: so many hypotheses, so few data. J Oral Maxillofac Surg. 2009; 67(5 Suppl):61–70.
36. Stopeck AT, Fizazi K, Body JJ, Brown JE, Carducci M, Diel I, et al. Safety of long-term denosumab therapy: results from the open label extension phase of two phase 3 studies in patients with metastatic breast and prostate cancer. Support Care Cancer. 2016; 24:447–55.
Full Text Links
  • KMJ
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr