Originally published as JCO Early Release 10.1200/JCO.2005.05.3744 on December 11 2006
Journal of Clinical Oncology, Vol 25, No 7 (March 1), 2007: pp. 829-836
© 2007 American Society of Clinical Oncology.
Zoledronic Acid Inhibits Adjuvant Letrozole–Induced Bone Loss in Postmenopausal Women With Early Breast Cancer
Adam Brufsky,
W. Graydon Harker,
J. Thaddeus Beck,
Robert Carroll,
Elizabeth Tan-Chiu,
Christopher Seidler,
John Hohneker,
Leo Lacerna,
Stephanie Petrone,
Edith A. Perez
From the Magee-Womens Hospital, University of Pittsburgh Cancer Institute, Pittsburgh, PA; Utah Cancer Specialists, Salt Lake City, UT; Highlands Oncology Group, Springdale, AK; North Florida Regional Medical Center, Gainesville; Cancer Research Network, Plantation; Mayo Clinic, Jacksonville, FL; Fallon Clinic Hematology Oncology, Worcester, MA; and Novartis Oncology, East Hanover, NJ
Address reprint requests to Adam Brufsky, MD, PhD, Magee-Womens Hospital, Ste 4628, 300 Halket St, Pittsburgh, PA 15123; e-mail: brufskyam{at}upmc.edu
Purpose Treatment with aromatase inhibitors decreases bone mineral density (BMD) and may increase the risk of fractures in postmenopausal women with early-stage breast cancer. The addition of zoledronic acid to adjuvant letrozole therapy may protect against bone loss.
Patients and Methods Patients receiving adjuvant letrozole were randomly assigned to receive either upfront or delayed-start zoledronic acid (4 mg intravenously every 6 months). The delayed group received zoledronic acid when lumbar spine (LS) or total hip (TH) T score decreased to less than –2.0 or when a nontraumatic fracture occurred. The primary end point of this study was to compare the change in LS BMD at month 12 between the groups. Secondary end points included change in TH BMD and changes in serum bone turnover markers at month 12.
Results The upfront and delayed groups each included 301 patients. At month 12, LS BMD was 4.4% higher in the upfront group than in the delayed group (95% CI, 3.7% to 5.0%; P < .0001), and TH BMD was 3.3% higher (95% CI, 2.8% to 3.8%; P < .0001). In the upfront group, mean serum N-telopeptide and bone-specific alkaline phosphatase concentrations decreased by 15.1% (P < .0001) and 8.8% (P = .0006), respectively, at month 12, whereas concentrations increased significantly in the delayed group by 19.9% (P = .013) and 24.3% (P < .0001), respectively.
Conclusion With 1 year of follow-up, results of the primary end point of the Zometa-Femara Adjuvant Synergy Trial (Z-FAST) indicate that upfront zoledronic acid therapy prevents bone loss in the LS in postmenopausal women receiving adjuvant letrozole for early-stage breast cancer.
published online ahead of print at www.jco.org on December 11, 2006.
Supported by Novartis Oncology, East Hanover, NJ.
Presented in part at the 27th Annual San Antonio Breast Cancer Symposium, December 8-11, 2004, San Antonio, TX; and the 41st Annual Meeting of the American Society of Clinical Oncology, May 13-17, 2005, Orlando, FL.
Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.
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