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Title: Immediate Administration of Zoledronic Acid Reduces Aromatase Inhibitor-Associated Bone Loss in Postmenopausal Women With Early Breast Cancer: 12-Month Analysis of the E-ZO-FAST Trial
Authors: Llombart, Antonio
Frassoldati, Antonio
Paija, Outi
Sleeboom, Harm Peter
Jerusalem, Guy
MEBIS, Jeroen 
Deleu, Ines
Miller, Joel
Schenk, Nora
Neven, Patrick
Issue Date: 2012
Source: CLINICAL BREAST CANCER, 12 (1), p. 40-48
Abstract: Aromatase inhibitors (AIs), an increasingly common adjuvant treatment option for postmenopausal women with hormone receptor-positive early breast cancer, are associated with bone loss that can impair patient quality of life. This study (E-ZO-FAST; Clinical Trials Identifier: NCT00171314) demonstrates that initiation of zoledronic acid therapy concurrent with adjuvant AI treatment improved skeletal health compared with zoledronic acid therapy initiated after deterioration of bone health. Background: Letrozole is a proven and effective adjuvant therapy in postmenopausal women with hormone receptor-positive (HR+) early breast cancer (EBC). As with other aromatase inhibitors (AIs), long-term letrozole administration is associated with decreased bone mineral density (BMD) and increased fracture risk. This study compared potential bone-protecting effects of immediate vs. delayed administration of zoledronic acid (ZOL) in patients with EBC receiving adjuvant letrozole. Patients and Methods: Patients with HR+ EBC in whom adjuvant letrozole treatment was initiated (2.5 mg/day for 5 years) were randomized to immediate ZOL treatment (immediate ZOL) or delayed ZOL treatment (delayed ZOL) (both at 4 mg every 6 months). Patients in the delayed ZOL group received ZOL only for a BMD T-score that decreased to < -2.0 (lumbar spine [LS] or total hip [TH]) or for fracture. The primary endpoint was percentage change in the LS BMD at month 12. Patients were stratified by established or recent postmenopausal status, baseline T-scores, and adjuvant chemotherapy history. Results: At 12 months, the LS BMD increased in the immediate ZOL group (+2.72%) but decreased in the delayed ZOL group (-2.71%); the absolute difference between groups was significant (5.43%; P < .0001). Across all subgroups, patients receiving immediate ZOL had significantly increased LS and TH BMD vs. those who received delayed ZOL (P < .0001). Differences in fracture incidence or disease recurrence could not be ascertained because of early data cutoff and low incidence of events. Adverse events were generally mild, transient, and consistent with the known safety profiles of both agents. Conclusion: Immediate ZOL administration effectively prevented BMD loss and increased BMD in postmenopausal women with HR+ EBC receiving adjuvant letrozole, regardless of BMD status at baseline. Clinical Breast Cancer, Vol. 12, No. 1, 40-8 (C) 2012 Elsevier Inc. All rights reserved.
Notes: [Llombart, Antonio] FISABIO Hosp Arnau de Vilanova, Valencia 46015, Spain. [Llombart, Antonio] Fdn Inst Valenciano Oncol, Valencia, Spain. [Frassoldati, Antonio] Univ Modena, Policlin, Sect Oncol, Dept Oncol Hematol & Lung Dis, I-41100 Modena, Italy. [Paija, Outi] Turku Univ Hosp, Dept Radiotherapy & Oncol, FIN-20520 Turku, Finland. [Sleeboom, Harm Peter] Hagaziekenhuis, The Hague, Netherlands. [Jerusalem, Guy] Domaine Univ, CHU Sart Tilman Liege, Liege, Belgium. [Miller, Joel; Schenk, Nora] Novartis Pharmaceut, E Hanover, NJ USA. [Neven, Patrick] UZ Leuven, Dept Obstet & Gynecol, Louvain, Belgium.
Keywords: Oncology;Aromatase inhibitor; Bone mineral density; Early breast cancer; Letrozole; Postmenopausal; Zoledronic acid
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ISSN: 1526-8209
e-ISSN: 1938-0666
DOI: 10.1016/j.clbc.2011.08.002
ISI #: 000299862300006
Category: A1
Type: Journal Contribution
Appears in Collections:Research publications

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