Skip to main content

Predictive factors for the efficacy of denosumab in postmenopausal Japanese women with non-metastatic breast cancer receiving adjuvant aromatase inhibitors: a combined analysis of two prospective clinical trials

Journal of Bone and Mineral Metabolism volume 37, pages 864–870 (2019)Cite this article

Abstract

Aromatase inhibitors (AIs) are the gold standard therapy for breast cancer in postmenopausal women. AI suppresses the conversion of androgens to estrogens; however, this results in osteopenia, osteoporosis, and bone fracture, thus reducing the patient’s quality of life. The use of adjuvant denosumab reduces the risk of clinical fractures in postmenopausal patients with breast cancer receiving AI. However, the efficacy of denosumab in the treatment of AI-associated bone loss has not been prospectively evaluated in Japan. In this study, we aimed to investigate the predictive factors for the efficacy of denosumab in postmenopausal patients with breast cancer treated with AI by analyzing the results of two prospective trials. The patients received 60 mg denosumab subcutaneously every 6 months. The primary endpoint was percentage change in lumbar spine bone mineral density (BMD) from baseline to month 12 in lumbar spine. Post hoc analysis and T tests were performed. A total of 205 patients were enrolled. At 12 and 24 months, the lumbar spine BMD increased by 5.6% [95% confidence interval (CI) 4.9–6.3] and 8.3% (95% CI 7.5–9.1), respectively. Subgroup analysis was conducted according to the time of AI therapy initiation, type of AI therapy, age, time since menopause, baseline body mass index, and BMD. The results showed that baseline lumbar and left femoral BMD was significantly associated with a percentage change in these sites, respectively. In addition, baseline left femoral BMD was also associated with a change in lumbar BMD. In conclusion, the baseline BMD in the lumbar spine was a predictive indicator for the efficacy of denosumab in this site and the baseline BMD in left femoral neck was a predictive indicator in lumbar spine and left femur.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2
Fig. 3

References

  1. Suzuki T, Yoshida H (2010) Low bone mineral density at femoral neck is a predictor of increased mortality in elderly Japanese women. Osteoporos Int 1:71–79

    Article  Google Scholar 

  2. Fisher ES, Baron JA, Malenka DJ, Barrett JA, Kniffin WD, Whaley FS, Bubolz TA (1991) Hip fracture incidence and mortality in New England. Epidemiology 2:116–122

    Article  CAS  PubMed  Google Scholar 

  3. Magaziner J, Simonsick EM, Kashner TM, Hebel JR, Kenzora JE (1989) Survival experience of aged hip fracture patients. Am J Public Health 79:274–278

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Pitto RP (1994) The mortality and social prognosis of hip fractures. A prospective multifactorial study. Int Orthop 18:109–113

    Article  CAS  PubMed  Google Scholar 

  5. Muraki S, Yamamoto S, Ishibashi H, Nakamura K (2006) Factors associated with mortality following hip fracture in Japan. J Bone Miner Metab 24:100–104

    Article  PubMed  PubMed Central  Google Scholar 

  6. Johansson C, Black D, Jonell O, Oden A, Mellstrom D (1998) Bone mineral density is a predictor of survival. Calcif Tissue Int 63:190–196

    Article  CAS  PubMed  Google Scholar 

  7. Kado DM, Browner WS, Palemo L, Nevitt MC, Genant HK, Cummings SR (1999) Vertebral fractures and mortality in older women. Arch Int Med 159:1215–1220

    Article  CAS  Google Scholar 

  8. Ensruud KE, Thompson DE, Cauley JA, Nevitt MC, Kado DM, Hochoberg MC, Santora AC, Black DM (2000) Prevalent vertebral deformities predict mortality and hospitalization in older women with low bone mass. J Am Geriat Soc 48:241–249

    Article  Google Scholar 

  9. Trivedi DP, Khaw KT (2001) Bone mineral density at the hip predicts mortality in elderly men. Osteoporos Int 12:259–265

    Article  CAS  PubMed  Google Scholar 

  10. Nguyen ND, Center JR, Eisman JA, Nguyen TV (2007) Bone loss, weight loss, and weight fluctuation predict mortality risk in elderly men and women. J Bone Miner Res 22:1147–1154

    Article  PubMed  Google Scholar 

  11. Hadji P, Aapro MS, Body JJ, Gnant M, Brandi ML et al (2017) Management of aromatase inhibitor-associated bone loss (AIBL) in postmenopausal women with hormone sensitive breast cancer: Joint position statement of the IOF, CABS, ECTS, IEG, ESCEO IMS, and SIOG. J Bone Oncol 7:1–12

    Article  PubMed  PubMed Central  Google Scholar 

  12. Nakatsukasa K, Koyama H, Ouchi Y, Sakaguchi K, Fujita Y, Matsuda T, Kato M, Konishi E, Taguchi T (2017) Effect of denosumab administration on low bone mineral density (T-score − 1.0 to − 2.5) in postmenopausal Japanese women receiving adjuvant aromatase inhibitors for non-metastatic breast cancer. J Bone Miner Metab. https://doi.org/10.1007/s00774-017-0884-x (Epub ahead of print)

    Article  PubMed  Google Scholar 

  13. Nakatsukasa K, Koyama H, Ouchi Y, Sakaguchi K, Fujita Y, Matsuda T, Kato M, Konishi E, Taguchi T (2018) Effects of denosumab on bone mineral density in Japanese women with osteoporosis treated with aromatase inhibitors for breast cancer. J Bone Miner Metab. https://doi.org/10.1007/s00774-018-0917-0 (Epub ahead of print)

    Article  PubMed  Google Scholar 

  14. Nakatsukasa K, Koyama H, Ouchi Y, Sakaguchi K, Fujita Y, Matsuda T, Kato M, Konishi E, Taguchi T (2018) Effect of denosumab on bone mineral density in Japanese women with osteopenia treated with aromatase inhibitors for breast cancer: subgroup analyses of a Phase II study. Ther Clin Risk Manag 14:1213–1218

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Nakatsukasa K, Koyama H, Ouchi Y, Ono H, Sakaguchi K et al (2018) The effect of denosumab on low bone mineral density (T-score − 1.0 to − 2.5) in postmenopausal Japanese women receiving adjuvant aromatase inhibitors for non-metastatic breast cancer: 24-month results. Breast Cancer. https://doi.org/10.1007/s12282-018-0896-y (Epub ahead of print)

    Article  PubMed  Google Scholar 

  16. Gnant M, Pfeiler G, Dubsky PC, Hubalek M, Greil R et al (2015) Adjuvant denosumab in breast cancer (ABCSG-18): a multicenter, randomized, double-blind, placebo-controlled trial. Lancet 386:433–443

    Article  CAS  PubMed  Google Scholar 

  17. Ellis GK, Bone HG, Chlebowski R, Paul D, Spadfora S, Smith J, Jun S (2008) Randomized trial of denosumab in patients receiving adjuvant aromatase inhibitors for nonmetastatic breast cancer. J Clin Oncol 26:4875–4882

    Article  CAS  PubMed  Google Scholar 

  18. Zebaze RM, Libanati C, Austin M, Ghasem-Zadeh A, Hanley DA, Zanchetta JR, Thomas T, Boutroy S, Bogado CE, Bilezikian JP, Seeman E (2014) Differing effects of denosumab and alendronate on cortical and trabecular bone. Bone 59:173–179

    Article  CAS  PubMed  Google Scholar 

  19. Kostenuik PJ, Smith SY, Jolette J, Schroeder J, Pyrah I, Ominsky MS (2011) Decreased bone remodeling and porosity are associated with improved bone strength in ovariectomized cynomolgus monkeys treated with denosumab, a fully human RANKL antibody. Bone 49:151–161

    Article  CAS  PubMed  Google Scholar 

  20. Devogelaer JP, Broll H, Correa-Rotter R, Cumming DC, De Deuxchaisnes CN et al (1996) Oral alendronate induces progressive increases in bone mass of the spine, hip, and total body over 3 years in postmenopausal women with osteoporosis. Bone 18:141–150

    Article  CAS  PubMed  Google Scholar 

  21. Tucci JR, Tonino RP, Emkey RD, Peverly CA, Kher U, Santora AC II (1996) Effect of three years of oral alendronate treatment in postmenopausal women with osteoporosis. Am J Med 101:488–501

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Affiliations

  1. Department of Endocrine and Breast Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan

    Katsuhiko Nakatsukasa, Yoshimi Ouchi, Kouichi Sakaguchi, Yoshifumi Fujita & Tetsuya Taguchi

  2. Nara City Hospital, Nara, Japan

    Hiroshi Koyama

  3. Saiseikai Kyoto Hospital, Kyoto, Japan

    Takayuki Matsuda

  4. Kato Breast Surgery Clinic, Kusatsu, Shiga, Japan

    Makoto Kato

  5. Department of Surgical Pathology, Kyoto Prefectural University of Medicine, Kyoto, Japan

    Eiichi Konishi

Authors
  1. Katsuhiko Nakatsukasa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hiroshi Koyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yoshimi Ouchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kouichi Sakaguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yoshifumi Fujita
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Takayuki Matsuda
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Makoto Kato
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Eiichi Konishi
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Tetsuya Taguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tetsuya Taguchi.

Ethics declarations

Conflict of interest

All authors declare that they have no conflicts of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

About this article

Verify currency and authenticity via CrossMark

Cite this article

Nakatsukasa, K., Koyama, H., Ouchi, Y. et al. Predictive factors for the efficacy of denosumab in postmenopausal Japanese women with non-metastatic breast cancer receiving adjuvant aromatase inhibitors: a combined analysis of two prospective clinical trials. J Bone Miner Metab 37, 864–870 (2019). https://doi.org/10.1007/s00774-018-00985-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00774-018-00985-8

Keywords

  • Breast cancer
  • Aromatase inhibitor
  • Denosumab
  • Predictive factor