Long-term effects of anastrozole on bone mineral density: Seven-year results from the ATAC trial

Abstract

587 Background: At a median follow-up of 100 months, the ATAC trial has established the long-term efficacy of anastrozole compared with tamoxifen. The study also demonstrates that, whilst adjuvant anastrozole is associated with higher fracture rates than tamoxifen during active treatment, after cessation of therapy there is a rapid decline in fracture rates in the anastrozole group to levels similar to those in the tamoxifen group. Examining the changes in bone mineral density (BMD) during the follow-up period provides additional important information on the skeletal health effects of anastrozole treatment following cessation of therapy. Methods: This randomized, prospective sub-study of the ATAC trial assessed BMD changes in postmenopausal women with invasive primary breast cancer receiving anastrozole (1 mg/day) or tamoxifen (20 mg/day) as adjuvant therapy for five years. Lumbar spine (L1-L4) and total hip BMD were assessed at baseline and after 1, 2, 5, 6, and 7 years using dual energy x-ray absorptiometry. Results: Two years after cessation of treatment, BMD measurements were available for 24 patients in the anastrozole group and 29 in the tamoxifen group. The table below shows the percentage change in BMD in each group (anastrozole vs. tamoxifen, **p<0.01, ***p<0.001). Conclusions: The increased bone loss seen with anastrozole compared with tamoxifen during the five-year adjuvant treatment period did not continue into the off-treatment follow-up period. A recovery of BMD at the lumbar spine and a slowing down in loss at the hip was observed in the anastrozole group. Treatment Anastrozole 0 to 5 years Tamoxifen 0 to 5 years Anastrozole 5 to 7 years Tamoxifen 5 to 7 years N 57 51 24 29 Lumbar spine, % (95% CI) -6.1*** (-10,7, -3.0) +2.8 (-1.4, 5.7) +4.0** (2.2, 5.9) -0.2 (-1.8, 1.5) Total hip, % (95% CI) -7.2*** (-12.4, -3.7) 0.7 (-2.5, 2.8) -0.9 (-2.3, 0.6) -2.4 (-3.7, 1.1) Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration AstraZeneca AstraZeneca