Originally published as JCO Early Release 10.1200/JCO.2005.02.7102 on December 11 2006
Journal of Clinical Oncology, Vol 25, No 7 (March 1), 2007: pp. 820-828
© 2007 American Society of Clinical Oncology.
Zoledronic Acid Prevents Cancer Treatment–Induced Bone Loss in Premenopausal Women Receiving Adjuvant Endocrine Therapy for Hormone-Responsive Breast Cancer: A Report From the Austrian Breast and Colorectal Cancer Study Group
Michael F.X. Gnant,
Brigitte Mlineritsch,
Gero Luschin-Ebengreuth,
Stephan Grampp,
Helmut Kaessmann,
Marianne Schmid,
Christian Menzel,
Jutta Claudia Piswanger-Soelkner,
Arik Galid,
Martina Mittlboeck,
Hubert Hausmaninger,
Raimund Jakesz
From the Departments of Surgery, Radiology, and Osteology; Core Unit for Medical Statistics and Informatics; and Division of Special Gynecology, General Hospital, Medical University of Vienna, Vienna; Departments of Internal Medicine III, and Nuclear Medicine and Endocrinology, Breast Center Salzburg, Paracelsus Private Medical University Salzburg, Salzburg; Department of Gynecology and Obstetrics; Department of Internal Medicine, Division of Oncology; and Department of Internal Medicine, Division of Endocrinology and Nuclear Medicine, Medical University Graz, Graz, Austria
Address reprint requests to Michael Gnant, MD, Medical University of Vienna, Department of Surgery, Währinger GürA-1090, Vienna, Austria; e-mail: michael.gnant{at}meduniwien.ac.at
Purpose Adjuvant therapy for breast cancer can be associated with decreased bone mineral density (BMD) that may lead to skeletal morbidity. This study examined whether zoledronic acid can prevent bone loss associated with adjuvant endocrine therapy in premenopausal patients.
Patients and Methods This study is a randomized, open-label, phase III, four-arm trial comparing tamoxifen (20 mg/d orally) and goserelin (3.6 mg every 28 days subcutaneously) ± zoledronic acid (4 mg intravenously every 6 months) versus anastrozole (1 mg/d orally) and goserelin ± zoledronic acid for 3 years in premenopausal women with hormone-responsive breast cancer. In a BMD subprotocol at three trial centers, patients underwent serial BMD measurements at 0, 6, 12, 24, and 36 months.
Results Four hundred one patients were included in the BMD subprotocol. Endocrine treatment without zoledronic acid led to significant (P < .001) overall bone loss after 3 years of treatment (BMD, –14.4% after 36 months; mean T score reduction, –1.4). Overall bone loss was significantly more severe in patients receiving anastrozole/goserelin (BMD, –17.3%; mean T score reduction, –2.6) compared with patients receiving tamoxifen/goserelin (BMD, –11.6%; mean T score reduction, –1.1). In contrast, BMD remained stable in zoledronic acid–treated patients (P < .0001 compared with endocrine therapy alone). No interactions with age or other risk factors were noted.
Conclusion Endocrine therapy caused significant bone loss that increased with treatment duration in premenopausal women with breast cancer. Zoledronic acid 4 mg every 6 months effectively inhibited bone loss. Regular BMD measurements and initiation of concomitant bisphosphonate therapy on evidence of bone loss should be considered for patients undergoing endocrine therapy.
published online ahead of print at www.jco.org on December 11, 2006.
Supported in part by AstraZeneca and Novartis Pharmaceuticals.
Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.
 CiteULike  Complore  Connotea  Del.icio.us  Digg  Facebook  Reddit  Technorati  Twitter What's this?
Related Editorials
- Bone Density in Breast Cancer: When to Intervene?
Julie R. Gralow
JCO 2007 0: 200712343
[Abstract]
- Bone Density in Breast Cancer: When to Intervene?
Julie R. Gralow
JCO 2007 25: 3194-3197
[Full Text]
This article has been cited by other articles:
|
|
|
|
 
M. Gnant, P. Blaha, P. Dubsky, R. Exner, F. Fitzal, E. Sporn, P. Panhofer, A. Dal Borgo, S. Bigenzahn, G. Steger, et al.
Review: Adjuvant bisphosphonates in endocrine-responsive breast cancer: what is their place in therapy?
Therapeutic Advances in Medical Oncology,
November 1, 2009;
1(3):
123 - 136.
[Abstract]
[PDF]
|
|
|
|
|
|
|
P. L. Bedard, J.-J. Body, and M. J. Piccart-Gebhart
Sowing the Soil for Cure? Results of the ABCSG-12 Trial Open a New Chapter in the Evolving Adjuvant Bisphosphonate Story in Early Breast Cancer
J. Clin. Oncol.,
September 1, 2009;
27(25):
4043 - 4046.
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. SIMMONS, E. AMIR, G. DRANITSARIS, M. CLEMONS, B. WONG, R. VEITH, and D. E.C. COLE
Altered Calcium Metabolism in Patients on Long-term Bisphosphonate Therapy for Metastatic Breast Cancer
Anticancer Res,
July 1, 2009;
29(7):
2707 - 2711.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Hackshaw, M. Baum, T. Fornander, B. Nordenskjold, A. Nicolucci, K. Monson, S. Forsyth, K. Reczko, U. Johansson, H. Fohlin, et al.
Long-term Effectiveness of Adjuvant Goserelin in Premenopausal Women With Early Breast Cancer
J Natl Cancer Inst,
March 4, 2009;
101(5):
341 - 349.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. L. Hines, B. A. Mincey, J. A. Sloan, S. P. Thomas, E. Chottiner, C. L. Loprinzi, M. D. Carlson, P. J. Atherton, M. Salim, and E. A. Perez
Phase III Randomized, Placebo-Controlled, Double-Blind Trial of Risedronate for the Prevention of Bone Loss in Premenopausal Women Undergoing Chemotherapy for Primary Breast Cancer
J. Clin. Oncol.,
March 1, 2009;
27(7):
1047 - 1053.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Gnant, B. Mlineritsch, W. Schippinger, G. Luschin-Ebengreuth, S. Postlberger, C. Menzel, R. Jakesz, M. Seifert, M. Hubalek, V. Bjelic-Radisic, et al.
Endocrine Therapy plus Zoledronic Acid in Premenopausal Breast Cancer
N. Engl. J. Med.,
February 12, 2009;
360(7):
679 - 691.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Saad, J. D. Adachi, J. P. Brown, L. A. Canning, K. A. Gelmon, R. G. Josse, and K. I. Pritchard
Cancer Treatment-Induced Bone Loss in Breast and Prostate Cancer
J. Clin. Oncol.,
November 20, 2008;
26(33):
5465 - 5476.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. K. Ellis, H. G. Bone, R. Chlebowski, D. Paul, S. Spadafora, J. Smith, M. Fan, and S. Jun
Randomized Trial of Denosumab in Patients Receiving Adjuvant Aromatase Inhibitors for Nonmetastatic Breast Cancer
J. Clin. Oncol.,
October 20, 2008;
26(30):
4875 - 4882.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. E. Lonning
Endocrine Therapy and Bone Loss in Breast Cancer: Time to Close in the RANK(L)?
J. Clin. Oncol.,
October 20, 2008;
26(30):
4859 - 4861.
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. L. Hershman, D. J. McMahon, K. D. Crew, S. Cremers, D. Irani, G. Cucchiara, L. Brafman, and E. Shane
Zoledronic Acid Prevents Bone Loss in Premenopausal Women Undergoing Adjuvant Chemotherapy for Early-Stage Breast Cancer
J. Clin. Oncol.,
October 10, 2008;
26(29):
4739 - 4745.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. R. Berenson, O. Yellin, R. V. Boccia, M. Flam, S.-F. Wong, O. Batuman, M. M. Moezi, D. Woytowitz, H. Duvivier, Y. Nassir, et al.
Zoledronic Acid Markedly Improves Bone Mineral Density for Patients with Monoclonal Gammopathy of Undetermined Significance and Bone Loss
Clin. Cancer Res.,
October 1, 2008;
14(19):
6289 - 6295.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. E. Lester, D. Dodwell, O. P. Purohit, S. A. Gutcher, S. P. Ellis, R. Thorpe, J. M. Horsman, J. E. Brown, R. A. Hannon, and R. E. Coleman
Prevention of Anastrozole-Induced Bone Loss with Monthly Oral Ibandronate during Adjuvant Aromatase Inhibitor Therapy for Breast Cancer
Clin. Cancer Res.,
October 1, 2008;
14(19):
6336 - 6342.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Saarto, L. Vehmanen, C. Blomqvist, and I. Elomaa
Ten-Year Follow-Up of 3 Years of Oral Adjuvant Clodronate Therapy Shows Significant Prevention of Osteoporosis in Early-Stage Breast Cancer
J. Clin. Oncol.,
September 10, 2008;
26(26):
4289 - 4295.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Gibson and C. L O'Bryant
Screening and management of osteoporosis in breast cancer patients on aromatase inhibitors
Journal of Oncology Pharmacy Practice,
September 1, 2008;
14(3):
139 - 145.
[Abstract]
[PDF]
|
|
|
|
|
|
|
M. T. Drake, B. L. Clarke, and S. Khosla
Bisphosphonates: Mechanism of Action and Role in Clinical Practice
Mayo Clin. Proc.,
September 1, 2008;
83(9):
1032 - 1045.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Hadji, J. -J. Body, M. S. Aapro, A. Brufsky, R. E. Coleman, T. Guise, A. Lipton, and M. Tubiana-Hulin
Practical guidance for the management of aromatase inhibitor-associated bone loss
Ann. Onc.,
August 1, 2008;
19(8):
1407 - 1416.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Brufsky, N. Bundred, R. Coleman, R. Lambert-Falls, R. Mena, P. Hadji, L. Jin, N. Schenk, S. Ericson, E. A. Perez, et al.
Integrated Analysis of Zoledronic Acid for Prevention of Aromatase Inhibitor-Associated Bone Loss in Postmenopausal Women with Early Breast Cancer Receiving Adjuvant Letrozole
Oncologist,
May 1, 2008;
13(5):
503 - 514.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Aapro, P. A. Abrahamsson, J. J. Body, R. E. Coleman, R. Colomer, L. Costa, L. Crino, L. Dirix, M. Gnant, J. Gralow, et al.
Guidance on the use of bisphosphonates in solid tumours: recommendations of an international expert panel
Ann. Onc.,
March 1, 2008;
19(3):
420 - 432.
[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]
|
|
|
|
|
|
|
A. M. Brufsky
Cancer Treatment-Induced Bone Loss: Pathophysiology and Clinical Perspectives
Oncologist,
February 1, 2008;
13(2):
187 - 195.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Aebi and M. Rabaglio
Overview of Current Approaches to Adjuvant Endocrine Therapy
ASCO Educational Book,
January 1, 2008;
2008(1):
9 - 13.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. E. Brown, S. P. Ellis, J. E. Lester, S. Gutcher, T. Khanna, O.-P. Purohit, E. McCloskey, and R. E. Coleman
Prolonged Efficacy of a Single Dose of the Bisphosphonate Zoledronic Acid
Clin. Cancer Res.,
September 15, 2007;
13(18):
5406 - 5410.
[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]
|
|
|
|
