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Effect of denosumab on bone mineral density in women receiving adjuvant aromatase inhibitors for non-metastatic breast cancer: subgroup analyses of a phase 3 study

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Abstract

Denosumab increased lumbar spine bone mineral density (BMD) versus placebo in a 2-year, randomized, placebo-controlled, phase 3 study of patients with hormone-receptor-positive, non-metastatic breast cancer and low bone mass who were receiving adjuvant aromatase inhibitor therapy. In subgroup analyses at 12 and 24 months, we evaluated factors (duration and type of aromatase inhibitor, tamoxifen use, age, time since menopause, body mass index, T-score) that might influence BMD at the lumbar spine, total hip, femoral neck, and 1/3 radius. Patients were randomized to receive placebo (n = 125) or 60 mg denosumab (n = 127) subcutaneously every 6 months. In all subgroups, 12 or 24 months’ treatment with denosumab was associated with larger BMD gains than placebo across multiple skeletal sites. Most increases were statistically significant (P < 0.05). Twice-yearly administration of denosumab, regardless of patient subgroup or skeletal site, resulted in consistent increases in BMD versus placebo at 12 and 24 months.

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Acknowledgments

This study was funded by Amgen Inc., Thousand Oaks, CA. This study is registered with ClinicalTrials.gov with the identifier NCT00089661. GK Ellis is an investigator in this study and has received research grants from Amgen, Abraxis, and Roche, and has been a speaker for Novartis. HG Bone is an investigator for Amgen, Merck, Zelos, Eli Lilly, Novartis, and Nordic Bioscience, and has been a consultant for Amgen, Osteologix, Nordic Bioscience, Merck, Zelos, Pfizer, Novartis, and GlaxoSmithKline; he has received speaker’s honoraria from Novartis. R. Chlebowski has been a consultant for AstraZeneca, Novartis, Genentech, Pfizer, Lilly, and Wyeth; he has received speaker’s honoraria from AstraZeneca, Abraxis, and Novartis. D. Paul and S. Spadafora have no conflicts of interest to disclose. M. Fan and D. Kim are employees of Amgen Inc. We thank Christine Gatchalian, PhD, of Amgen Inc., and Linda Melvin, BA, for writing assistance.

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Authors and Affiliations

  1. Seattle Cancer Care Alliance, 825 Eastlake Avenue East, Mail Stop G3-200, Seattle, WA, 98109-1023, USA

    Georgiana K. Ellis

  2. Michigan Bone & Mineral Clinic, Detroit, MI, USA

    Henry G. Bone

  3. UCLA Medical Center, Torrance, CA, USA

    Rowan Chlebowski

  4. US Oncology, Houston, TX, USA

    Devchand Paul

  5. Rocky Mountain Cancer Centers, Denver, CO, USA

    Devchand Paul

  6. Algoma Regional Cancer Program, Sault Ste. Marie, ON, Canada

    Silvana Spadafora

  7. Amgen Inc., Thousand Oaks, CA, USA

    Michelle Fan & Dennis Kim

Authors
  1. Georgiana K. Ellis
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  2. Henry G. Bone
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  3. Rowan Chlebowski
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  4. Devchand Paul
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  5. Silvana Spadafora
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  6. Michelle Fan
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  7. Dennis Kim
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Correspondence to Georgiana K. Ellis.

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Ellis, G.K., Bone, H.G., Chlebowski, R. et al. Effect of denosumab on bone mineral density in women receiving adjuvant aromatase inhibitors for non-metastatic breast cancer: subgroup analyses of a phase 3 study. Breast Cancer Res Treat 118, 81–87 (2009). https://doi.org/10.1007/s10549-009-0352-y

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  • DOI: https://doi.org/10.1007/s10549-009-0352-y

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