Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Medical Oncology
Published in: Medical Oncology 3/2008

01-09-2008 | Review

Bisphosphonate treatment and radiotherapy in metastatic breast cancer

Authors: A. Ugur Ural, Ferit Avcu, Yusuf Baran

Published in: Medical Oncology | Issue 3/2008

Login to get access

Abstract

Patients with advanced breast cancer frequently develop metastasis to bone. Bone metastasis results in intractable pain and high risk of pathologic fractures due to osteolysis. The treatment of breast cancer patients with bone metastases requires a multidisciplinary approach. Radiotherapy is an established treatment for metastatic bone pain. It may be delivered either as a localized low dose treatment for localized bone pain or systemically for more widespread symptoms. Bisphosphonates have been shown to reduce morbidity and bone pain from bone metastases when given to patients with metastatic bone disease. In vivo studies indicate that early bisphosphonates administration in combination with radiotherapy improves remineralization and restabilization of osteolytic bone metastases in animal tumor models. This review focused on a brief discussion about biology of bone metastases, the effects of radiotherapy and bisphosphonate therapy, and possible mechanisms of combination therapy in metastatic breast cancer patients.
Literature
1.
Jemal A, et al. Cancer statistics, 2005. CA Cancer J Clin. 2005;55(1):10–30.PubMed
2.
Coleman RE. Metastatic bone disease: clinical features, pathophysiology and treatment strategies. Cancer Treat Rev. 2001;27(3):165–76.PubMedCrossRef
3.
Cicek M, Oursler MJ. Breast cancer bone metastasis and current small therapeutics. Cancer Metastasis Rev. 2006;25(4):635–44.PubMedCrossRef
4.
Hsu H, et al. Tumour necrosis factor receptor family member RANK mediates osteoclast differentiation and activation induced by osteoprotegerin ligand. Proc Natl Acad Sci USA. 1999;96(7):3540–45.PubMedCrossRef
5.
Lacey DL, et al. Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell. 1998;93(2):165–76.PubMedCrossRef
6.
Simonet WS, et al. Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell. 1997;89(2):309–19.PubMedCrossRef
7.
Guise TA, et al. Parathyroid hormone-related protein (PTHrP)(1–139) isoform is efficiently secreted in vitro and enhances breast cancer metastasis to bone in vivo. Bone. 2002;30(5):670–6.PubMedCrossRef
8.
Pederson L, et al. Identification of breast cancer cell line-derived paracrine factors that stimulate osteoclast activity. Cancer Res. 1999;59(22):5849–55.PubMed
9.
Mercer RR, Miyasaka C, Mastro AM. Metastatic breast cancer cells suppress osteoblast adhesion and differentiation. Clin Exp Metastasis. 2004;21(5):427–35.PubMedCrossRef
10.
Mastro AM, et al. Breast cancer cells induce osteoblast apoptosis: a possible contributor to bone degradation. J Cell Biochem. 2004;91(2):265–76.PubMedCrossRef
11.
Hoskin PJ. Bisphosphonates and radiation therapy for palliation of metastatic bone disease. Cancer Treat Rev. 2003;29(4):321–7.PubMedCrossRef
12.
Luini A, et al. The evolution of the conservative approach to breast cancer. Breast. 2007;16(2):120–9.PubMedCrossRef
13.
Vukmirovic-Popovic S, et al. Morphological, histomorphometric, and microstructural alterations in human bone metastasis from breast carcinoma. Bone. 2002;31(4):529–35.PubMedCrossRef
14.
Krempien R, et al. Combination of early bisphosphonate administration and irradiation leads to improved remineralization and restabilization of osteolytic bone metastases in an animal tumor model. Cancer. 2003;98(6):1318–24.PubMedCrossRef
15.
Pandit-Taskar N, Batraki M, Divgi CR. Radiopharmaceutical therapy for palliation of bone pain from osseous metastases. J Nucl Med. 2004;45(8):1358–65.PubMed
16.
Li L, Story M, Legerski RJ. Cellular responses to ionizing radiation damage. Int J Radiat Oncol Biol Phys. 2001;49(4):1157–62.PubMedCrossRef
17.
Hoskin PJ, Ford HT, Harmer CL. Hemibody irradiation (HBI) for metastatic bone pain in two histologically distinct groups of patients. Clin Oncol (R Coll Radiol). 1989;1(2):67–9.
18.
Hoskin PJ, et al. A prospective randomised trial of 4 Gy or 8 Gy single doses in the treatment of metastatic bone pain. Radiother Oncol. 1992;23(2):74–8.PubMedCrossRef
19.
Arcangeli G, et al. The responsiveness of bone metastases to radiotherapy: the effect of site, histology and radiation dose on pain relief. Radiother Oncol. 1989;14(2):95–101.PubMedCrossRef
20.
Hoskin PJ, et al. Effect of local radiotherapy for bone pain on urinary markers of osteoclast activity. Lancet. 2000;355(9213):1428–9.PubMedCrossRef
21.
Ural AU, Avcu F. Evolving therapeutic role of bisphosphonates in multiple myeloma. Br J Cancer. 2005;93(2):267–8.PubMedCrossRef
22.
Sato M, et al. Bisphosphonate action. Alendronate localization in rat bone and effects on osteoclast ultrastructure. J Clin Invest. 1991;88(6):2095–105.PubMedCrossRef
23.
Bukowski JF, Dascher CC, Das H. Alternative bisphosphonate targets and mechanisms of action. Biochem Biophys Res Commun. 2005;328(3):746–50.PubMedCrossRef
24.
25.
Ural AU, Avcu F. Bisphosphonates may potentiate radiation effects: a new approach in cancer treatment? Biochem Biophys Res Commun. 2005;336(2):373–4.PubMedCrossRef
26.
Li X, et al. Inhibition of protein geranylgeranylation and RhoA/RhoA kinase pathway induces apoptosis in human endothelial cells. J Biol Chem. 2002;277(18):15309–16.PubMedCrossRef
27.
Carteni G, et al. Efficacy and safety of zoledronic acid in patients with breast cancer metastatic to bone: a multicenter clinical trial. Oncologist. 2006;11(7):841–8.PubMedCrossRef
28.
Vinholes JJ, et al. Relationships between biochemical and symptomatic response in a double-blind randomised trial of pamidronate for metastatic bone disease. Ann Oncol. 1997;8(12):1243–50.PubMedCrossRef
29.
Ural AU, et al. The bisphosphonate zoledronic acid induces cytotoxicity in human myeloma cell lines with enhancing effects of dexamethasone and thalidomide. Int J Hematol. 2003;78(5):443–9.PubMed
30.
Dhodapkar MV, et al. Anti-myeloma activity of pamidronate in vivo. Br J Haematol. 1998;103(2):530–2.PubMedCrossRef
31.
Kunzmann V, et al. Stimulation of gammadelta T cells by aminobisphosphonates and induction of antiplasma cell activity in multiple myeloma. Blood. 2000;96(2):384–92.PubMed
32.
33.
Avcu F, et al. The bisphosphonate zoledronic acid inhibits the development of plasmacytoma induced in BALB/c mice by intraperitoneal injection of pristane. Eur J Haematol. 2005;74(6):496–500.PubMedCrossRef
34.
Magnetto S, et al. Additive antitumor activities of taxoids in combination with the bisphosphonate ibandronate against invasion and adhesion of human breast carcinoma cells to bone. Int J Cancer. 1999;83(2):263–9.PubMedCrossRef
35.
van der Pluijm G, et al. Bisphosphonates inhibit the adhesion of breast cancer cells to bone matrices in vitro. J Clin Invest. 1996;98(3):698–705.PubMedCrossRef
36.
Ural AU, et al. In vitro synergistic cytoreductive effects of zoledronic acid and radiation on breast cancer cells. Breast Cancer Res. 2006;8(4):R52.PubMedCrossRef
37.
Woodward JK, et al. Combined effects of zoledronic acid and doxorubicin on breast cancer cell invasion in vitro. Anticancer Drugs. 2005;16(8):845–54.PubMedCrossRef
38.
Jagdev SP, et al. The bisphosphonate, zoledronic acid, induces apoptosis of breast cancer cells: evidence for synergy with paclitaxel. Br J Cancer. 2001;84(8):1126–34.PubMedCrossRef
39.
Ural AU, Avcu F. Additive/synergistic anti-tumoral effects of the combination of docetaxel and zoledronic acid on prostate cancer cells: possible mechanisms? Acta Oncol. 2006;45(4):491–2.PubMedCrossRef
40.
Algur E, Macklis RM, Hafeli UO. Synergistic cytotoxic effects of zoledronic acid and radiation in human prostate cancer and myeloma cell lines. Int J Radiat Oncol Biol Phys. 2005;61(2):535–42.PubMed
41.
Ural AU, Avcu F. Radiosensitizing effect of zoledronic acid in small cell lung cancer. Lung Cancer 2005;50(2):271–2.PubMedCrossRef
42.
Kurdoglu B, et al. Apoptosis as a predictor of paclitaxel-induced radiosensitization in human tumor cell lines. Clin Cancer Res. 1999;5(9):2580–7.PubMed
43.
McKenna WG, Muschel RJ. Targeting tumor cells by enhancing radiation sensitivity. Genes Chromosomes Cancer. 2003;38(4):330–8.PubMedCrossRef
44.
Bernhard EJ, et al. The farnesyltransferase inhibitor FTI-277 radiosensitizes H-ras-transformed rat embryo fibroblasts. Cancer Res. 1996;56(8):1727–30.PubMed
45.
Journe F, et al. Sequence- and concentration-dependent effects of acute and long-term exposure to the bisphosphonate ibandronate in combination with single and multiple fractions of ionising radiation doses in human breast cancer cell lines. Clin Exp Metastasis. 2006;23(2):135–47.PubMedCrossRef
46.
Hillner BE, et al. American Society of Clinical Oncology 2003 update on the role of bisphosphonates and bone health issues in women with breast cancer. J Clin Oncol 2003.;21(21):4042–57.PubMedCrossRef
47.
Kouloulias V, et al. Radiotherapy in conjunction with intravenous infusion of 180 mg of disodium pamidronate in management of osteolytic metastases from breast cancer: clinical evaluation, biochemical markers, quality of life, and monitoring of recalcification using assessments of gray-level histogram in plain radiographs. Int J Radiat Oncol Biol Phys. 2003;57(1):143–57.PubMed
Metadata
Title
Bisphosphonate treatment and radiotherapy in metastatic breast cancer
Authors
A. Ugur Ural
Ferit Avcu
Yusuf Baran
Publication date
01-09-2008
Publisher
Humana Press Inc
Published in
Medical Oncology / Issue 3/2008
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-008-9044-4

Other articles of this Issue 3/2008

Medical Oncology 3/2008 Go to the issue

REVIEW

Understanding and management of male breast cancer: a critical review

Original Paper

Functional characterization of the HOXB13 promoter region

CASE

Primary mediastinal large B-cell lymphoma mimicking liposarcoma

Original Paper

Inhibition of 7,12-dimethylbenzanthracene-induced skin tumors by a nutrient mixture

Original Paper

Renal safety of zoledronic acid administration beyond 24 months in breast cancer patients with bone metastases

Book Review

Prostate cancer
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Heart Failure Video

Year in Review: Heart failure and cardiomyopathies

Watch now

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits