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Effect of denosumab on low bone mineral density in postmenopausal Japanese women receiving adjuvant aromatase inhibitors for non-metastatic breast cancer: 24-month results

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Abstract

Background

Aromatase inhibitors (AI) have been established as the gold-standard therapy for postmenopausal patients. Worldwide, adjuvant denosumab at a dose of 60 mg twice per year reduces the risk of clinical fractures in postmenopausal patients with breast cancer who received AI. However, the efficacy of denosumab in the treatment of AI-associated bone loss had not been prospectively evaluated in Japan. Previously, we reported the 12-month effect of denosumab in Japanese patients for the first time; the primary endpoint was the change in the percentage of bone mineral density (BMD) of the lumbar spine from baseline to 12 months.

Methods

This secondary follow-up study prospectively evaluated the change in the percentage of BMD of the lumbar spine from baseline to 24 months. Postmenopausal women with early-stage, histologically confirmed, hormone receptor-positive, invasive breast cancer who were receiving or scheduled to receive AI were included. Denosumab was administered subcutaneously on day 1 of the study and then 6, 12, 18, and 24 months. The lumbar spine and bilateral femoral neck BMD was measured at baseline and 6, 12, 18, and 24 months.

Results

At 18 and 24 months, the lumbar spine BMD increased by 5.9 and 7.0%, respectively. The femoral neck BMD also increased. Grade ≥ 2 hypocalcemia, osteonecrosis of the jaw, and atypical femoral fractures did not occur.

Conclusions

Our prospective study showed that semiannual treatment with denosumab was associated with continuously increased BMD in Japanese women receiving adjuvant AI therapy for up to 24 months, regardless of prior AI treatment.

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Acknowledgements

This study was supported in part by Grants-in-Aid for Scientific Research from the Japanese Breast Cancer Society.

Author information

Authors and 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, Hisako Ono, Kouichi Sakaguchi & Tetsuya Taguchi

  2. Molecular-Targeting Cancer Prevention, Kyoto Prefectural University of Medicine, Kyoto, Japan

    Hisako Ono

  3. Surgical Pathology, Kyoto Prefectural University of Medicine, Kyoto, Japan

    Eiichi Konishi

  4. Nara City Hospital, Nara, Japan

    Hiroshi Koyama

  5. Saiseikai Kyoto Hospital, Kyoto, Japan

    Takayuki Matsuda

  6. Kato Breast Surgery Clinic, Kyoto, Japan

    Makoto Kato

  7. Department of Breast, Tokyo Medical University, Tokyo, Japan

    Takashi Ishikawa & Kimito Yamada

  8. Department of Radiology, Tokyo Medical University, Tokyo, Japan

    Mana Yoshimura

  9. Department of Breast Oncology, Seirei Hamamatsu General Hospital, Hamamatsu, Japan

    Kei Koizumi

  10. Department of Surgery, Wakayama Medical University Kihoku Hospital, Wakayama, Japan

    Teruhisa Sakurai

  11. Department of Breast Surgery, National Hospital Organization Kure Medical Center and Chugoku Cancer Center, Kure-City, Hiroshima, Japan

    Hideo Shigematsu

  12. Department of Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan

    Shunji Takahashi & Shinichiro Taira

  13. Department of Breast Surgery, National Hospital Organization Chiba Medical Center, Yokohama City University Medical Center, Tokyo, Japan

    Masato Suzuki

  14. Department of Breast and Thyroid Surgery, Yokohama City University Medical Center, Yokohama, 232-0024, Japan

    Kazutaka Narui

  15. Department of Breast and Endocrine Surgery, Tokai University School of Medicine, Tokyo, Japan

    Naoki Niikura

  16. Department of Breast Surgical Oncology, Hirosaki Municipal Hospital, Hirosaki, Japan

    Yoshie Hasegawa

  17. Akasaka Miura Clinic, Tokyo, Japan

    Daishu Miura

Authors
  1. Katsuhiko Nakatsukasa
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  2. Hiroshi Koyama
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  7. Makoto Kato
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  8. Takashi Ishikawa
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  9. Kimito Yamada
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  10. Mana Yoshimura
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  11. Kei Koizumi
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  12. Teruhisa Sakurai
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  15. Shinichiro Taira
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  16. Masato Suzuki
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  17. Kazutaka Narui
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  18. Naoki Niikura
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  19. Yoshie Hasegawa
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  20. Daishu Miura
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  21. Eiichi Konishi
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  22. Tetsuya Taguchi
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Consortia

Collaborative Study Group of Scientific Research of the Japanese Breast Cancer Society

Corresponding author

Correspondence to Tetsuya Taguchi.

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Conflict of interest

Dr Tetsuya Taguchi received Research grant from Chugai, Taiho and Daiichi Sankyo. Dr Shunji Takahashi received Research grant from Daiichi Sankyo. Other authors declare that they have no conflict of interest.

Ethics approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standard.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Nakatsukasa, K., Koyama, H., Ouchi, Y. et al. Effect of denosumab on low bone mineral density in postmenopausal Japanese women receiving adjuvant aromatase inhibitors for non-metastatic breast cancer: 24-month results. Breast Cancer 26, 106–112 (2019). https://doi.org/10.1007/s12282-018-0896-y

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  • DOI: https://doi.org/10.1007/s12282-018-0896-y

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