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Bisphosphonates: Prevention of Bone Metastases in Breast Cancer

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Prevention of Bone Metastases

Part of the book series: Recent Results in Cancer Research ((RECENTCANCER,volume 192))

Abstract

Disease recurrence and distant metastases remain challenging for patients with breast cancer despite advances in early diagnosis, surgical expertise, and adjuvant therapy. Bone is the most common site for breast cancer metastasis, and the bone microenvironment plays a crucial role in harboring disseminated tumor cells (DTCs), a putative source of late relapse in and outside bone. Therefore, agents that affect bone metabolism might not only prevent the development of bone lesions but also provide meaningful reductions in the risk of relapse both in bone and beyond. Bisphosphonates bind to mineralized bone surfaces and are ingested by osteoclasts, wherein they inhibit osteolysis, thereby preventing the release of growth factors from the bone matrix. Therefore, the bone microenvironment becomes less conducive to survival and growth of DTCs and bone lesion formation. Recent trials of zoledronic acid in the adjuvant setting in breast cancer have demonstrated reduced disease recurrence in bone and other sites in premenopausal and postmenopausal women with early breast cancer. Based on the proven effect of bone protection during adjuvant endocrine therapy, new treatment guidelines recommend the routine use of bisphosphonates to prevent bone loss during adjuvant therapy, which may likely become the standard practice.

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Abbreviations

ABCSG:

Austrian Breast and Colorectal Cancer Study Group

AE:

Adverse event

AI:

Aromatase inhibitor

ANA:

Anastrozole

BCINIS:

Breast Cancer in Northern Israel Study

β-CTX:

Beta C-terminal telopeptide of type I collagen

BM:

Bone metastases

BMD:

Bone mineral density

BP:

Bisphosphonate

CI:

Confidence interval

CLO:

Clodronate

CTCs:

Circulating tumor cells

CTIBL:

Cancer treatment-induced bone loss

DFS:

Disease-free survival

DTCs:

Disseminated tumor cells

ER:

Estrogen receptor

ESMO:

European Society for Medical Oncology

HCM:

Hypercalcemia of malignancy

HER2:

Human epidermal growth factor receptor 2

HR:

Hazard ratio

IBA:

Ibandronate

LET:

Letrozole

LN:

Lymph node

NCIC CTG:

National Cancer Institute of Canada Clinical Trials Group

NNT:

Number needed to treat

NR:

None reported

NS:

Not significant

ONJ:

Osteonecrosis of the jaw

OS:

Overall survival

SRE:

Skeletal-related events

TAM:

Tamoxifen

VEGF:

Vascular endothelial growth factor

WHI-OS:

Women’s Health Initiative Observational Study

Z-/ZO-/E-ZO-FAST:

Zometa-Femara Adjuvant Synergy Trials

ZOL:

Zoledronic acid

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Acknowledgments

Financial support for medical editorial assistance was provided by Novartis Pharmaceuticals. We thank Catherine Browning, PhD, ProEd Communications, Inc.®, for her medical editorial assistance with this manuscript.

Conflict of Interest

Dr. Gnant has served on advisory boards for and received consulting and lecture fees from AstraZeneca and Novartis, as well as lecture fees and research support from Roche, Schering, Pfizer, Novartis, AstraZeneca, sanofi-aventis, and Amgen. Dr. Dubsky has received honoraria for lectures and advisory boards from Novartis, Pfizer, AstraZeneca, and Roche, and other remuneration (travel) from Novartis, Roche, AstraZeneca, and Pfizer. Dr. Hadji has received honoraria, unrestricted educational grants, and research funding from Amgen, AstraZeneca, Eli Lilly, GlaxoSmithKline, Novartis, Pfizer, Roche, and sanofi-aventis.

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  1. Department of Surgery, Comprehensive Cancer Center Vienna, Medical University of Vienna, Waehringer Guertel 18-20, A-1090, Wien, Austria

    Michael Gnant & Peter Dubsky

  2. Department of Gynecology, Gynecological Endocrinology and Oncology, Philipps-University of Marburg, Marburg, Germany

    Peyman Hadji

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  1. Michael Gnant
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  2. Peter Dubsky
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  3. Peyman Hadji
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Correspondence to Michael Gnant .

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  1. , Dept. of Medical Oncology, Kantonsspital St. Gallen, Rorschacherstr. 95, St. Gallen, 9007, Switzerland

    Markus Joerger

  2. Chirurgische Klinik, Abt. Allgemeine Chirurgie, Universitätsklinikum Wien, Währinger Gürtel 18-20, Wien, 1090, Austria

    Michael Gnant

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Gnant, M., Dubsky, P., Hadji, P. (2012). Bisphosphonates: Prevention of Bone Metastases in Breast Cancer. In: Joerger, M., Gnant, M. (eds) Prevention of Bone Metastases. Recent Results in Cancer Research, vol 192. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-21892-7_3

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  • DOI: https://doi.org/10.1007/978-3-642-21892-7_3

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