Bisphosphonates: Prevention of Bone Metastases in Breast Cancer

Chapter
Part of the Recent Results in Cancer Research book series (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.

Keywords

Adjuvant therapy Anticancer Bisphosphonate Bone metastases Breast cancer Cancer prevention Clodronate Zoledronic acid 

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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Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  1. 1.Department of SurgeryComprehensive Cancer Center Vienna, Medical University of ViennaWienAustria
  2. 2.Department of GynecologyGynecological Endocrinology and Oncology, Philipps-University of MarburgMarburgGermany

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