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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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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