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Efficacy of zoledronic acid in postmenopausal Japanese women with early breast cancer receiving adjuvant letrozole: 12-month results

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Abstract

Aromatase inhibitor-associated bone loss has not been proved in the Japanese or Asian women. The aim of this study was to evaluate an upfront or delayed strategy of bone protection therapy with zoledronic acid administered at 4 mg every 6 months in postmenopausal Japanese women with early breast cancer to compare with results of the Z-FAST and ZO-FAST studies in western countries. Postmenopausal women with hormone receptor positive early breast cancer receiving adjuvant letrozole were randomly assigned to receive either upfront or delayed-start zoledronic acid (4 mg intravenously every 6 months). The delayed group received zoledronic acid when lumbar spine (L2–L4) bone mineral density (BMD) decreased to less than young adult mean −2.0SD or when a nontraumatic fracture occurred. The primary endpoint of this study was to compare the percent change in L1–L4 BMD at 12 months between the groups. Secondary endpoints included percent changes in L2–L4 and total hip (TH) BMD. The upfront and delayed groups included 94 and 95 patients, respectively. At 12 months, L1–L4, L2–L4, and TH BMD significantly decreased by 2.0, 2.4, and 2.4%, respectively, in the delayed group. L1–L4 BMD was 4.9% higher in the upfront group than in the delayed group (95% CI 3.9–5.8%; p < 0.001). L2–L4 BMD was 5.6% higher (95% CI 4.5–6.6%; p < 0.001), and TH BMD was 4.4% higher (95% CI 3.3–5.4%; p < 0.001). At 12 months, upfront zoledronic acid therapy prevented bone loss in postmenopausal Japanese women who were receiving adjuvant letrozole, confirming the Z-/ZO-FAST study results in western populations.

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Acknowledgments

We thank all the participating investigators, Dr. M. Hosoda (Hokkaido University Hospital), Dr. Y. Koibuchi, Dr. R. Nagaoka, Dr. N. Rokutanda, Dr. H. Tokiniwa (Gunma University Hospital), Dr. H. Bando (Tsukuba University Hospital), Dr. M. Satoh, Dr. H. Ohsawa (Jichi Medical University Hospital), Dr. A. Ohsaki (Saitama Medical University), Dr. K. Yamada, Dr. H. Kaise (Tokyo Medical University), Dr. Y. Itoh, Dr. N. Tokudome, Dr. E. Makita, Dr. K. Tada, Dr. S. Nishimura, Dr. K. Iijima, Dr. Y. Miyagi, Dr. H. Morizono, Dr. K. Kimura (Cancer Institute Hospital of JFCR), Dr. T. Kuwayama, Dr. M. Mori (St. Luke’s International Hospital), Dr. M. Saitoh, Dr. E. Tokuda (Juntendo University Hospital), Dr. H. Isaka, Dr. K. Imi (Kyorin University Hospital), Dr. H. Jinno (Keio University Hospital), Dr. Y. Tamaki, Dr. S.J. Kim, Dr. T. Nakayama, Dr. K. Shimazu (Osaka University Hospital), Dr. Y. Hashimoto (Kinki University Hospital), Dr. K. Nakashima (Kawasaki Medical University), Dr. S. Murakami, Dr. N. Masumoto, Dr. J. Emi (Hiroshima University Hospital), Dr. H. Iwase, Dr. Y. Yamamoto (Kumamoto University Hospital) for their contribution, and Miss M. Yamazaki and Miss C. Suitsu (Cancer Institute Hospital of JFCR) for data management.

Conflict of interest

ST and SN are consultants, and have received remuneration and research support from Novartis.

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Authors and Affiliations

  1. Department of Medical Oncology and Hematology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan

    Shunji Takahashi

  2. Department of Breast Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan

    Takuji Iwase

  3. Department of Breast Oncology, Tokyo Medical University Hospital, Tokyo, Japan

    Norio Kohno

  4. Department of Breast and Thyroid Surgery, Yokohama City University Medical Center, Yokohama, Japan

    Takashi Ishikawa

  5. Department of Breast and Endocrine Surgery, Osaka University Hospital, Osaka, Japan

    Tetsuya Taguchi & Shinzaburo Noguchi

  6. First Department of Surgery, Hokkaido University Hospital, Sapporo, Japan

    Masato Takahashi

  7. Department of Breast and Endocrine Surgery, Gunma University Hospital, Gunma, Japan

    Jun Horiguchi

  8. Department of Breast Surgery, St Luke’s International Hospital, Tokyo, Japan

    Seigo Nakamura

  9. Department of Breast and General Surgery, Jichi Medical University Hospital, Tochigi, Japan

    Yasuo Hozumi

  10. Kawasaki Medical School, Okayama, Japan

    Masao Fukunaga

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  1. Shunji Takahashi
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Correspondence to Shunji Takahashi.

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Takahashi, S., Iwase, T., Kohno, N. et al. Efficacy of zoledronic acid in postmenopausal Japanese women with early breast cancer receiving adjuvant letrozole: 12-month results. Breast Cancer Res Treat 133, 685–693 (2012). https://doi.org/10.1007/s10549-012-1973-0

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