Bone effects of adjuvant tamoxifen (T), letrozole (L), or L plus zoledronic acid (Z) in early breast cancer (EBC): The phase III HOBOE study.

517 Background: Treatment with L can reduce bone mineral density (BMD) in patients (pts) with EBC. However, the addition of Z may protect against bone loss. Methods: We performed a 1:1:1 randomized phase III trial to compare the bone effects of adjuvant T, L or L+Z in pre- and postmenopausal pts with hormone-receptor positive EBC. Premenopausal pts also received triptorelin. Primary end point was T-score at lumbar spine (LST) measured by DXA-scan 1 year after randomization. The study had 80% power to detect a 0.35 effect size. Two comparisons were planned: L vs T and L+Z vs L; for each one, a linear model was applied to test treatment effect adjusted by age, menopausal status, previous chemotherapy and baseline LST. Two exploratory analyses were done to test whether baseline body mass index (BMI) and 6-month estradiol level were associated with L vs T effect. NCT00412022. Results: From March ‘04 to December ‘09, 483 patients were enrolled; 459 (247 pre- and 212 postmenopausal) were available for primary a...