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Prognostic factors for skeletal complications from metastatic bone disease in breast cancer

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Abstract

Skeletal morbidity is common in patients with bone metastases from breast cancer (BC) and can undermine patients’ functional independence and quality of life. Previously defined prognostic factors may not reflect current treatment standards and the use of antiresorptive therapies. We report a comprehensive multivariate analysis of potential prognostic factors for skeletal-related events (SREs) using data from a phase III, randomized study of zoledronic acid in patients with bone metastases from BC. The trial evaluated the number and timing of SREs (pathologic fracture, palliative radiotherapy to bone, surgery to bone to treat or prevent a fracture, and spinal cord compression) and assessed variables for prognostic significance in univariate and multivariate Cox-regression analyses. Continuous variables were categorized with predefined cutpoints. All associations with P < 0.05 were considered significant. A total of 444 zoledronic acid-treated patients with assessments of biochemical markers of bone metabolism and complete baseline variable data were included. Significant baseline prognostic factors for occurrence of a first SRE by multivariate analyses included age, pain score, prior history of an SRE, predominant lesion type, elevated bone-specific alkaline phosphatase, and lactate dehydrogenase. Prior fracture was found to be prognostic in a reduced multivariate analysis of time to first fracture, but not for time to first palliative radiotherapy. In conclusion, this model identified several prognostic factors that may be useful in routine clinical care. Validation of these factors in a separate dataset and generation of a prognostic risk score are recommended next steps.

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Abbreviations

BAP:

Bone-specific alkaline phosphatase

BC:

Breast cancer

BPI:

Brief pain inventory

CI:

Confidence interval

Cr:

Creatinine

ECOG PS:

Eastern Cooperative Oncology Group performance status

LDH:

Lactate dehydrogenase

NTX:

N-telopeptide of type I collagen.

RR:

Relative risk

SD:

Standard deviation

SGOT:

Serum glutamic oxaloacetic transaminase

SRE:

Skeletal-related event

ULN:

Upper limit of normal

ZOL:

Zoledronic acid

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Acknowledgments

We are grateful to Cancer Research UK for support for J.E.B. We thank Carol Sledz, PhD, from ProEd Communications, Inc.®, for her medical editorial assistance with this manuscript, unrestricted funding for which was provided by Novartis Pharmaceuticals Corporation, East Hanover, New Jersey.

Conflicts of interest statement

Janet Brown has received speakers bureau honoraria from Novartis and Amgen and has served as a consultant and/or on advisory boards for Novartis, Amgen, Roche, and Bristol-Myers Squibb. Richard Cook has served as a consultant and/or on advisory boards for Novartis and Abbott. Allan Lipton has received commercial research grants from Novartis, Monogram Biosciences, and Oncogene Science; has received speakers bureau honoraria from Novartis, Amgen, and Genentech; has served as a consultant and/or on advisory boards for Novartis, Amgen, Galapagos, Acceleron Pharm, and has given expert testimony for Novartis. Luis Costa has received speakers bureau honoraria from Novartis and has served as a consultant and/or on advisory boards for Novartis and Amgen. Robert Coleman has received other commercial support from Novartis; speakers bureau honoraria from Novartis and Amgen; has served as a consultant and/or on advisory boards for Novartis, Amgen, Pfizer, and Roche; and has previously given expert testimony on the behalf of Novartis.

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Authors and Affiliations

  1. Cancer Research UK Clinical Centre, University of Leeds, Leeds, UK

    Janet E. Brown

  2. Cancer Research Centre, University of Sheffield, Weston Park Hospital, Sheffield, UK

    Janet E. Brown & Robert E. Coleman

  3. University of Waterloo, Waterloo, ON, Canada

    Richard J. Cook

  4. Milton S. Hershey Medical Center, Pennsylvania State University, Hershey, PA, USA

    Allan Lipton

  5. Hospital de Santa Maria, Lisbon, Portugal

    Luis Costa

  6. Cancer Research UK Clinical Centre, St. James’ University Hospital, JIF Building, Beckett Street, Leeds, LS9 7TF, UK

    Janet E. Brown

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  1. Janet E. Brown
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  2. Richard J. Cook
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  3. Allan Lipton
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  4. Luis Costa
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  5. Robert E. Coleman
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Correspondence to Janet E. Brown.

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Brown, J.E., Cook, R.J., Lipton, A. et al. Prognostic factors for skeletal complications from metastatic bone disease in breast cancer. Breast Cancer Res Treat 123, 767–779 (2010). https://doi.org/10.1007/s10549-010-0981-1

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  • DOI: https://doi.org/10.1007/s10549-010-0981-1

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