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Effects of zoledronic acid on bone mineral density in premenopausal women receiving neoadjuvant or adjuvant therapies for HR+ breast cancer: the ProBONE II study

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Abstract

Summary

The effects of bisphosphonates on altered bone turnover marker (BTM) levels associated with adjuvant endocrine or chemotherapy in early breast cancer have not been systematically investigated. In ProBONE II, zoledronic acid decreased these elevated BTM levels and increased bone mineral density (BMD) during adjuvant therapy, consistent with its antiresorptive effects.

Introduction

Adjuvant chemotherapy or endocrine therapy for early hormone receptor-positive breast cancer (HR+ BC) is associated with rapid BMD loss and altered BTM levels. Adjuvant bisphosphonate studies demonstrated BMD increases, but did not investigate BTM effects. The randomized, double-blind, ProBONE II study investigated the effect of adjuvant zoledronic acid (ZOL) on BMD and BTM in premenopausal women with early HR+ BC.

Methods

Seventy premenopausal women with early HR+ BC received adjuvant chemotherapy and/or endocrine therapy plus ZOL (4 mg IV every 3 months) or placebo for 24 months. Primary endpoint was change in lumbar spine BMD at 24 months versus baseline. Secondary endpoints included femoral neck and total femoral BMD changes, changes in BTM, and safety.

Results

Lumbar spine BMD increased 3.14 % from baseline to 24 months in ZOL-treated participants versus a 6.43 % decrease in placebo-treated participants (P < 0.0001). Mean changes in T- and Z-scores, and femoral neck and total femoral BMD, showed similar results. Bone resorption marker levels decreased ∼55 % in ZOL-treated participants versus increases up to 65 % in placebo-treated participants (P < 0.0001 for between-group differences). Bone formation marker (procollagen I N-terminal propeptide) levels decreased ∼57 % in ZOL-treated participants versus increases up to 45 % in placebo-treated participants (P < 0.0001 for between-group differences). Adverse events were consistent with the established ZOL safety profile and included one case of osteonecrosis of the jaw after a tooth extraction.

Conclusions

Adding ZOL to adjuvant therapy improved BMD, reduced BTM levels, and was well tolerated in premenopausal women with early HR+ BC receiving adjuvant chemotherapy and/or endocrine therapy.

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Acknowledgement

Financial support for medical editorial assistance was provided by Novartis Pharmaceuticals Corporation. We thank Elaine Wacholtz, PhD, ProEd Communications, Inc., for medical editorial assistance with this manuscript. This research was made possible by grant support from Novartis.

Conflicts of interest

P. Hadji has received honoraria and unrestricted educational grants from Amgen, AstraZeneca, Eli Lilly, GlaxoSmithKline, Novartis, Pfizer, and Roche. A. Kauka and M. Bauer have no conflicts of interest. M. Ziller has received honoraria and unrestricted educational grants from Eli Lilly, Gedeon Richter Pharma GmbH, Jenapharm GmbH and Co. KG, Dr. Kade GmbH, Madaus/Rottapharm GmbH, Novartis, and Pfizer. K. Birkholz, M. Baier, and M. Muth are employees of Novartis Pharma GmbH.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Philipps-University of Marburg, Baldingerstrasse, 35033, Marburg, Germany

    P. Hadji, A. Kauka, M. Ziller & M. Bauer

  2. Novartis Pharma GmbH, BU Oncology, Roonstrasse 25, 90429, Nuernberg, Germany

    K. Birkholz, M. Baier & M. Muth

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  1. P. Hadji
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Correspondence to P. Hadji.

Additional information

Preliminary data were presented at the following: 7th European Breast Cancer Conference, 24–27 March 2010, Poster 14; 2011 CTRC-AACR San Antonio Breast Cancer Symposium; 6–10 December 2011, Poster P2-19-03; 12th International Conference on Cancer-Induced Bone Disease, 15–17 November 2012, Poster P76; Deutscher 2012 Krebskongress, 22–25 February 2012; Osteoonkologie, 23–24 March 2012, Poster P14; and Société Française de Sénologie et de Pathologie Mammaire, 14–16 November 2012.

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Hadji, P., Kauka, A., Ziller, M. et al. Effects of zoledronic acid on bone mineral density in premenopausal women receiving neoadjuvant or adjuvant therapies for HR+ breast cancer: the ProBONE II study. Osteoporos Int 25, 1369–1378 (2014). https://doi.org/10.1007/s00198-013-2615-z

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  • DOI: https://doi.org/10.1007/s00198-013-2615-z

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