Originally published as JCO Early Release 10.1200/JCO.2003.08.017 on September 8 2003
Journal of Clinical Oncology, Vol 21, Issue 21
(November), 2003: 4042-4057
© 2003 American Society for Clinical Oncology
American Society of Clinical Oncology 2003 Update on the Role of Bisphosphonates and Bone Health Issues in Women With Breast Cancer
Bruce E. Hillner,
James N. Ingle,
Rowan T. Chlebowski,
Julie Gralow,
Gary C. Yee,
Nora A. Janjan,
Jane A. Cauley,
Brent A. Blumenstein,
Kathy S. Albain,
Allan Lipton,
Susan Brown
From the American Society of Clinical Oncology, Alexandria, Virginia.
Address reprint requests to American Society of Clinical Oncology, Cancer Policy and Clinical Affairs, 1900 Duke Street, Suite 200, Alexandria, VA 22314; e-mail: guidelines{at}asco.org.
Purpose: To update the 2000 ASCO guidelines on the role of bisphosphonates in women with breast cancer and address the subject of bone health in these women.
Results: For patients with plain radiographic evidence of bone destruction, intravenous pamidronate 90 mg delivered over 2 hours or zoledronic acid 4 mg over 15 minutes every 3 to 4 weeks is recommended. There is insufficient evidence supporting the efficacy of one bisphosphonate over the other. Starting bisphosphonates in women who demonstrate bone destruction through imaging but who have normal plain radiographs is considered reasonable treatment. Starting bisphosphonates in women with only an abnormal bone scan but without evidence of bone destruction is not recommended. The presence or absence of bone pain should not be a factor in initiating bisphosphonates.
In patients with a serum creatinine less than 3.0 mg/dL (265 µmol/L), no change in dosage, infusion time, or interval is required. Infusion times less than 2 hours with pamidronate or less than 15 minutes with zoledronic acid should be avoided. Creatinine should be monitored before each dose of either agent in accordance with US Food and Drug Administration (FDA) labeling.
Oncology professionals, especially medical oncologists, need to take an expanded role in the routine and regular assessment of the osteoporosis risk in women with breast cancer. The panel recommends an algorithm for patient management to maintain bone health.
Conclusion: Bisphosphonates provide a supportive, albeit expensive and nonlife-prolonging, benefit to many patients with bone metastases. Current research is focusing on bisphosphonates as adjuvant therapy. Although new data addressing when to stop therapy, alternative doses or schedules for administration, and how to best coordinate bisphosphonates with other palliative therapies are needed, they are not currently being investigated.
Adopted on May 30, 2003 by the American Society of Clinical Oncology.
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[Abstract]
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|
 |
|

|
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|
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[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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13(7):
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[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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Risedronate Prevents Bone Loss in Breast Cancer Survivors: A 2-Year, Randomized, Double-Blind, Placebo-Controlled Clinical Trial
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26(16):
2644 - 2652.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. H. Giordano, S. Fang, Z. Duan, Y.-F. Kuo, G. N. Hortobagyi, and J. S. Goodwin
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Oncologist,
May 1, 2008;
13(5):
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[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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Oncologist,
May 1, 2008;
13(5):
503 - 514.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
H. B. Muss, D. Tu, J. N. Ingle, S. Martino, N. J. Robert, J. L. Pater, T. J. Whelan, M. J. Palmer, M. J. Piccart, L. E. Shepherd, et al.
Efficacy, Toxicity, and Quality of Life in Older Women With Early-Stage Breast Cancer Treated With Letrozole or Placebo After 5 Years of Tamoxifen: NCIC CTG Intergroup Trial MA.17
J. Clin. Oncol.,
April 20, 2008;
26(12):
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[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. Crivellari, Z. Sun, A. S. Coates, K. N. Price, B. Thurlimann, H. Mouridsen, L. Mauriac, J. F. Forbes, R. J. Paridaens, M. Castiglione-Gertsch, et al.
Letrozole Compared With Tamoxifen for Elderly Patients With Endocrine-Responsive Early Breast Cancer: The BIG 1-98 Trial
J. Clin. Oncol.,
April 20, 2008;
26(12):
1972 - 1979.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
N. Raje, S.-B. Woo, K. Hande, J. T. Yap, P. G. Richardson, S. Vallet, N. Treister, T. Hideshima, N. Sheehy, S. Chhetri, et al.
Clinical, Radiographic, and Biochemical Characterization of Multiple Myeloma Patients with Osteonecrosis of the Jaw
Clin. Cancer Res.,
April 15, 2008;
14(8):
2387 - 2395.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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Case 9-2008 -- A 65-Year-Old Woman with a Nonhealing Ulcer of the Jaw
N. Engl. J. Med.,
March 20, 2008;
358(12):
1283 - 1291.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P Hadji
Menopausal symptoms and adjuvant therapy-associated adverse events
Endocr. Relat. Cancer,
March 1, 2008;
15(1):
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[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Parton and I. E. Smith
Controversies in the Management of Patients With Breast Cancer: Adjuvant Endocrine Therapy in Premenopausal Women
J. Clin. Oncol.,
February 10, 2008;
26(5):
745 - 752.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
N. U. Lin and E. P. Winer
Advances in Adjuvant Endocrine Therapy for Postmenopausal Women
J. Clin. Oncol.,
February 10, 2008;
26(5):
798 - 805.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. M. Brufsky
Cancer Treatment-Induced Bone Loss: Pathophysiology and Clinical Perspectives
Oncologist,
February 1, 2008;
13(2):
187 - 195.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
H. S. Rugo
The breast cancer continuum in hormone-receptor positive breast cancer in postmenopausal women: evolving management options focusing on aromatase inhibitors
Ann. Onc.,
January 1, 2008;
19(1):
16 - 27.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
I. Sekine, M. Sumi, and N. Saijo
Local Control of Regional and Metastatic Lesions and Indication for Systemic Chemotherapy in Patients with Non-Small Cell Lung Cancer
Oncologist,
January 1, 2008;
13(suppl_1):
21 - 27.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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Letter to the editor: Does pamidronate enhance the analgesic effect of radiotherapy? A randomized trail
Palliative Medicine,
December 1, 2007;
21(8):
719 - 720.
[PDF]
|
 |
|

|
 |

|
 |
 
T. Bao and N. E. Davidson
How We Maintain Bone Health in Early-Stage Breast Cancer Patients on Aromatase Inhibitors
J. Oncol. Pract,
November 1, 2007;
3(6):
323 - 325.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
H. J. Burstein and E. P. Winer
Aromatase Inhibitors and Arthralgias: A New Frontier in Symptom Management for Breast Cancer Survivors
J. Clin. Oncol.,
September 1, 2007;
25(25):
3797 - 3799.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. B. Goodman, W. Jiranek, E. Petrow, and A. W. Yasko
The Effects of Medications on Bone
J. Am. Acad. Ortho. Surg.,
August 1, 2007;
15(8):
450 - 460.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. R. Gralow
Bone Density in Breast Cancer: When to Intervene?
J. Clin. Oncol.,
August 1, 2007;
25(22):
3194 - 3197.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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Oral ibandronate is as active as intravenous zoledronic acid for reducing bone turnover markers in women with breast cancer and bone metastases
Ann. Onc.,
July 1, 2007;
18(7):
1165 - 1171.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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N. Engl. J. Med.,
June 14, 2007;
356(24):
2505 - 2513.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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Zoledronic Acid Inhibits Adjuvant Letrozole-Induced Bone Loss in Postmenopausal Women With Early Breast Cancer
J. Clin. Oncol.,
March 1, 2007;
25(7):
829 - 836.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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Assessment of renal toxicity and osteonecrosis of the jaws in patients receiving zoledronic acid for bone metastasis
Ann. Onc.,
March 1, 2007;
18(3):
556 - 560.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. D Krueger, P. M West, M. Sargent, A. E Lodolce, and A S. Pickard
Bisphosphonate-Induced Osteonecrosis of the Jaw
Ann. Pharmacother.,
February 1, 2007;
41(2):
276 - 284.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. Eastell
Breast Cancer and the Risk of Osteoporotic Fracture: A Paradox
J. Clin. Endocrinol. Metab.,
January 1, 2007;
92(1):
42 - 43.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. L de Lemos, S. C Taylor, J. B Barnett, F. Hu, A. Levin, V. Moravan, and S. E O'Reilly
Renal safety of 1-hour pamidronate infusion for breast cancer and multiple myeloma patients: comparison between clinical trials and population-based database
Journal of Oncology Pharmacy Practice,
December 1, 2006;
12(4):
193 - 199.
[Abstract]
[PDF]
|
 |
|

|
 |

|
 |
 
A. J. Chien and P. E. Goss
Aromatase Inhibitors and Bone Health in Women With Breast Cancer
J. Clin. Oncol.,
November 20, 2006;
24(33):
5305 - 5312.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. A. Guise
Bone Loss and Fracture Risk Associated with Cancer Therapy
Oncologist,
November 1, 2006;
11(10):
1121 - 1131.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. J. Clemons, G. Dranitsaris, W. S. Ooi, G. Yogendran, T. Sukovic, B. Y.L. Wong, S. Verma, K. I. Pritchard, M. Trudeau, and D. E.C. Cole
Phase II Trial Evaluating the Palliative Benefit of Second-Line Zoledronic Acid in Breast Cancer Patients With Either a Skeletal-Related Event or Progressive Bone Metastases Despite First-Line Bisphosphonate Therapy
J. Clin. Oncol.,
October 20, 2006;
24(30):
4895 - 4900.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. E. Coleman
Clinical features of metastatic bone disease and risk of skeletal morbidity.
Clin. Cancer Res.,
October 15, 2006;
12(20):
6243s - 6249s.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J.-J. Body
Breast cancer: bisphosphonate therapy for metastatic bone disease.
Clin. Cancer Res.,
October 15, 2006;
12(20):
6258s - 6263s.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
G Sanna, L Preda, R Bruschini, M Cossu Rocca, S Ferretti, L Adamoli, E Verri, L Franceschelli, A Goldhirsch, and F Nole
Bisphosphonates and jaw osteonecrosis in patients with advanced breast cancer
Ann. Onc.,
October 1, 2006;
17(10):
1512 - 1516.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. R. Smith
Bisphosphonates for Metastatic Bone Disease -- Too Much of a Good Thing?
IBMS BoneKEy,
September 1, 2006;
3(9):
24 - 27.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. T. Chlebowski
Aromatase inhibitors and breast cancer treatment.
JAMA,
August 9, 2006;
296(6):
651 - 651.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. E. Come
Aromatase Inhibitors and Breast Cancer Treatment--Reply
JAMA,
August 9, 2006;
296(6):
651 - 651.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. Van den Wyngaert, M. T. Huizing, and J. B. Vermorken
Bisphosphonates and osteonecrosis of the jaw: cause and effect or a post hoc fallacy?
Ann. Onc.,
August 1, 2006;
17(8):
1197 - 1204.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Botteman, V. Barghout, J. Stephens, J. Hay, J. Brandman, and M. Aapro
Cost effectiveness of bisphosphonates in the management of breast cancer patients with bone metastases
Ann. Onc.,
July 1, 2006;
17(7):
1072 - 1082.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. D. Ryan and P. E. Goss
Adjuvant Hormonal Therapy in Peri- and Postmenopausal Breast Cancer
Oncologist,
July 1, 2006;
11(7):
718 - 731.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
G. Carteni, R. Bordonaro, F. Giotta, V. Lorusso, S. Scalone, V. Vinaccia, R. Rondena, and D. Amadori
Efficacy and Safety of Zoledronic Acid in Patients with Breast Cancer Metastatic to Bone: A Multicenter Clinical Trial
Oncologist,
July 1, 2006;
11(7):
841 - 848.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. Tanvetyanon and P. J. Stiff
Management of the adverse effects associated with intravenous bisphosphonates
Ann. Onc.,
June 1, 2006;
17(6):
897 - 907.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. B. Michaud and S. Goodin
Cancer-treatment-induced bone loss, part 1
Am. J. Health Syst. Pharm.,
March 1, 2006;
63(5):
419 - 430.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J.-J. Body, T. Facon, R. E. Coleman, A. Lipton, F. Geurs, M. Fan, D. Holloway, M. C. Peterson, and P. J. Bekker
A Study of the Biological Receptor Activator of Nuclear Factor-{kappa}B Ligand Inhibitor, Denosumab, in Patients with Multiple Myeloma or Bone Metastases from Breast Cancer
Clin. Cancer Res.,
February 15, 2006;
12(4):
1221 - 1228.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. N. Ingle
Adjuvant Endocrine Therapy for Postmenopausal Women with Early Breast Cancer
Clin. Cancer Res.,
February 1, 2006;
12(3):
1031s - 1036s.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. Van Poznak
Osteonecrosis of the Jaw
J. Oncol. Pract,
January 1, 2006;
2(1):
3 - 4.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Clemons, G. Dranitsaris, D. Cole, and M. C. Gainford
Too Much, Too Little, Too Late to Start Again? Assessing the Efficacy of Bisphosphonates in Patients with Bone Metastases from Breast Cancer.
Oncologist,
January 1, 2006;
11(3):
227 - 233.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. Crandall and J. P. Pregler
Update in Women's Health
Ann Intern Med,
December 6, 2005;
143(11):
823 - 829.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. Melisi, R. Caputo, V. Damiano, R. Bianco, B. M. Veneziani, A R. Bianco, S. De Placido, F. Ciardiello, and G. Tortora
Zoledronic acid cooperates with a cyclooxygenase-2 inhibitor and gefitinib in inhibiting breast and prostate cancer
Endocr. Relat. Cancer,
December 1, 2005;
12(4):
1051 - 1058.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Bamias, E. Kastritis, C. Bamia, L. A. Moulopoulos, I. Melakopoulos, G. Bozas, V. Koutsoukou, D. Gika, A. Anagnostopoulos, C. Papadimitriou, et al.
Osteonecrosis of the Jaw in Cancer After Treatment With Bisphosphonates: Incidence and Risk Factors
J. Clin. Oncol.,
December 1, 2005;
23(34):
8580 - 8587.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. A. MIGLIORATI, J. CASIGLIA, J. EPSTEIN, P. L. JACOBSEN, M. A. SIEGEL, and S.-B. WOO
Managing the care of patients with bisphosphonate-associated osteonecrosis: An American Academy of Oral Medicine position paper
J Am Dent Assoc,
December 1, 2005;
136(12):
1658 - 1668.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. E. Denes and P. D. Ryan
Case 24-2005: A Woman with Estrogen-Receptor-Positive Breast Cancer.
N. Engl. J. Med.,
November 24, 2005;
353(21):
2304 - 2305.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. D. Michaelson and M. R. Smith
Bisphosphonates for Treatment and Prevention of Bone Metastases
J. Clin. Oncol.,
November 10, 2005;
23(32):
8219 - 8224.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
V. Guarneri, S. Donati, M. Nicolini, S. Giovannelli, R. D'Amico, and P. F. Conte
Renal Safety and Efficacy of i.v. Bisphosphonates in Patients with Skeletal Metastases Treated for up to 10 Years
Oncologist,
November 1, 2005;
10(10):
842 - 848.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J.-J. Body
Bisphosphonates in Metastatic Bone Disease: Renal Safety Matters
Oncologist,
October 1, 2005;
10(suppl_1):
1 - 2.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. Bell
Efficacy of Ibandronate in Metastatic Bone Disease: Review of Clinical Data
Oncologist,
October 1, 2005;
10(suppl_1):
8 - 13.
[Abstract]
[Full Text]
[PDF]
|
 |
| |