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Effect of Anastrozole on Bone Mineral Density: 5-Year Results From the Anastrozole, Tamoxifen, Alone or in Combination Trial 18233230

Richard Eastell, Judith E. Adams, Robert E. Coleman, Anthony Howell, Rosemary A. Hannon, Jack Cuzick, John R. Mackey, Matthias W. Beckmann, Glen Clack

From the Academic Unit of Bone Metabolism, University of Sheffield; Cancer Research Centre, Weston Park Hospital, Sheffield; Department of Diagnostic Radiology, University of Manchester; Christie Hospital National Health Service Trust, Manchester; Wolfson Institute of Preventive Medicine, London; AstraZeneca, Cheshire, United Kingdom; Cross Cancer Institute, Edmonton, Alberta, Canada; Universität Erlangen-Nurnberg, Erlangen, Germany

Corresponding author: Richard Eastell, MD, Metabolic Bone Centre, Sorby Wing, Northern General Hospital, Herries Rd, Sheffield, S5 7AU United Kingdom; e-mail: r.eastell{at}sheffield.ac.uk

Purpose The Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial (median follow-up, 68 months) has shown that adjuvant anastrozole has superior efficacy and better tolerability than tamoxifen. However, anastrozole reduces circulating estrogen, and low estradiol levels are associated with decreased bone mineral density (BMD) and increased fracture risk. It is therefore important to understand the effects of long-term aromatase inhibitor therapy on BMD.

Patients and Methods This prospective substudy of the ATAC trial assessed BMD changes in postmenopausal women with invasive primary breast cancer receiving anastrozole (1 mg/d) or tamoxifen (20 mg/d) as adjuvant therapy for 5 years. Lumbar spine and total hip BMD were assessed at baseline and after 1, 2, and 5 years.

Results One hundred ninety-seven women from the monotherapy arms of the ATAC trial were recruited onto the bone substudy, and 108 were included in the primary analysis. Among anastrozole-treated patients, there was a decrease in median BMD from baseline to 5 years in lumbar spine (–6.08%) and total hip (–7.24%) compared with the tamoxifen group (lumbar spine, +2.77%; total hip, +0.74%). No patients with normal BMD at baseline became osteoporotic at 5 years.

Conclusion Anastrozole is associated with accelerated bone loss over the 5-year treatment period. However, although patients with pre-existing osteopenia are likely to require monitoring and bone-protection strategies, patients with normal BMD would not appear to require monitoring beyond the recommendation for healthy postmenopausal women. The effect of anastrozole on bone should be weighed against its superior efficacy and better tolerability profile versus tamoxifen in the main ATAC trial.

Supported in part by AstraZeneca Grants No. RF11494, R/116920-1, RF831144, RF104903, RF105658, RF105659, RF109529, RF104892, and RF110304.

Preliminary data from this study have previously been published in: Eastell R, Hannon RA, Cuzick J, et al: Effect of an aromatase inhibitor on BMD and bone turnover markers: 2-year results of the Anastrozole, Tamoxifen, Alone or in Combination (ATAC) Trial (18233230). J Bone Miner Res 21:1215-1223, 2006.

Presented in part at the 24th Annual Meeting of the American Society for Bone and Mineral Research, September 21-24, 2002, San Antonio, TX; the 27th European Society for Medical Oncology Congress, October 18-22, 2002, Nice, France; the 25th Annual Meeting of the American for Bone and Mineral Research, September 19-23, 2003, San Antonio, TX; the 26th Annual San Antonio Breast Cancer Symposium, December 3-6, 2003, San Antonio, TX; the 4th European Breast Cancer Conference, March 16-20, 2004, Hamburg, Germany; the 42nd American Society for Clinical Oncology Annual Meeting, June 2-6, 2006, Atlanta, GA; and the 33rd European Symposium on Calcified Tissues, May 10-14, 2006, Prague, Czech Republic.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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