Dr Eastell is a member of the Steering Committee at ATAC and is a consultant to AstraZeneca. Drs Eastell and Hannon receive honoraria and funding from Astrazeneca. Dr Hannon also receives honoraria from Pfizer Inc. Dr Cuzick is a statistical consultant for AstraZeneca. Dr Dowsett holds consultancies with and receives funding from Novartis and AstraZeneca. Dr Clack holds stock ownership in and is employed by AstraZeneca. All other authors state that they do not have any conflicts of interest.
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)
Article first published online: 22 MAY 2006
Copyright © 2006 ASBMR
Journal of Bone and Mineral Research
Volume 21, Issue 8, pages 1215–1223, August 2006
How to Cite
Eastell, R., Hannon, R. A., Cuzick, J., Dowsett, M., Clack, G. and Adams, J. E. (2006), 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. doi: 10.1359/jbmr.060508
- Issue published online: 4 DEC 2009
- Article first published online: 22 MAY 2006
- Manuscript Accepted: 12 MAY 2006
- Manuscript Revised: 7 MAY 2006
- Manuscript Received: 10 DEC 2005
- bone remodeling
Aromatase inhibitors reduce estrogen levels in postmenopausal women with breast cancer. Residual estrogen is an important determinant of bone turnover. Adjuvant anastrozole was associated with significant BMD loss and increased bone remodeling, whereas tamoxifen reduced bone marker levels.
Introduction: In the Anastrozole, Tamoxifen, Alone or in Combination (ATAC) trial after a median follow-up of 68 months, a significant improvement in disease-free survival was observed with anastrozole treatment (hazard ratio [HR], 0.87; 95% CI, 0.78–0.97; p = 0.01). Anastrozole was also associated with tolerability benefits compared with tamoxifen, but with higher fracture rates. The HR of anastrozole compared with tamoxifen after 60 months of treatment was 1.49 (95% CI, 1.25–1.77).
Materials and Methods: This prospectively designed subprotocol (n = 308) of ATAC assessed changes in BMD and bone turnover markers in postmenopausal women with invasive primary breast cancer receiving anastrozole 1 mg/day, tamoxifen 20 mg/day, or combination treatment with both agents for 5 years. Patients with osteoporosis were excluded (osteopenia permitted at the investigators discretion). Lumbar spine and total hip BMD was assessed at baseline and after 1 and 2 years; bone turnover markers (serum C-telopeptide, urinary N-telopeptide [NTX], free deoxypyridinoline, serum procollagen type-1 N-propeptide, bone alkaline phosphatase [ALP]) were assessed at baseline and after 3, 6, and 12 months. Results were expressed as median percentage change.
Results: After 2 years of anastrozole treatment, BMD was lost at lumbar spine (median 4.1% loss) and total hip (median 3.9% loss) sites; increases of 2.2% and 1.2%, respectively, were observed with tamoxifen. After 1 year of anastrozole treatment, increased bone remodeling was observed (NTX, +15%; 95% CI, 3–25%; bone ALP, +20%; 95% CI, 14–25%); decreased bone remodeling was observed with tamoxifen (NTX, −52%; 95% CI, −62% to −33%; bone ALP, −16%; 95% CI, −24% to −11%).
Conclusions: Anastrozole is associated with significant BMD loss and a small increase in bone turnover, whereas tamoxifen (and the combination) is associated with increased BMD and decreased remodeling. These data may explain the increased fracture risk observed with anastrozole treatment in the ATAC trial. The impact of anastrozole on bone should be weighed against its overall superior efficacy and tolerability as observed in the main ATAC trial.