Bone effect of adjuvant tamoxifen, letrozole or letrozole plus zoledronic acid in early-stage breast cancer: the randomized phase 3 HOBOE study
F Nuzzo, C Gallo, S Lastoria, M Di Maio, M C Piccirillo, A Gravina, G Landi, E Rossi, C Pacilio, V Labonia, F Di Rella, A Bartiromo, G Buonfanti, G De Feo, G Esposito, R D'Aniello, P Maiolino, S Signoriello, E De Maio, V Tinessa, G Colantuoni, M De Laurentiis, M D'Aiuto, M Di Bonito, G Botti, P Giordano, G Daniele, A Morabito, N Normanno, A de Matteis, F Perrone, F Nuzzo, C Gallo, S Lastoria, M Di Maio, M C Piccirillo, A Gravina, G Landi, E Rossi, C Pacilio, V Labonia, F Di Rella, A Bartiromo, G Buonfanti, G De Feo, G Esposito, R D'Aniello, P Maiolino, S Signoriello, E De Maio, V Tinessa, G Colantuoni, M De Laurentiis, M D'Aiuto, M Di Bonito, G Botti, P Giordano, G Daniele, A Morabito, N Normanno, A de Matteis, F Perrone
Abstract
Background: To measure bone mineral density (BMD) reduction produced by letrozole as compared with tamoxifen and the benefit of the addition of zoledronic acid.
Patients and methods: A phase 3 trial comparing tamoxifen, letrozole or letrozole+zoledronic acid in patients with hormone receptor-positive early breast cancer was conducted; triptorelin was given to premenopausal patients. Two comparisons were planned: letrozole versus tamoxifen and letrozole+zoledronic acid versus letrozole. Primary end point was the difference in 1-year change of T-score at lumbar spine (LTS) measured by dual energy X-ray absorptiometry scan.
Results: Out of 483 patients enrolled, 459 were available for primary analyses. Median age was 50 (range 28-80). The estimated mean difference (95% confidence interval [CI]) in 1-year change of LTS was equal to -0.30 (95% CI -0.44 to -0.17) in the letrozole versus tamoxifen comparison (P<0.0001) and to +0.60 (95% CI +0.46 to +0.77) in the letrozole+zoledronic acid versus letrozole comparison (P<0.0001). Bone damage by letrozole decreased with increasing baseline body mass index in premenopausal, but not postmenopausal, patients (interaction test P=0.004 and 0.47, respectively).
Conclusions: In the HOBOE (HOrmonal BOne Effects) trial, the positive effect of zoledronic acid on BMD largely counteracts damage produced by letrozole as compared with tamoxifen. Letrozole effect is lower among overweight/obese premenopausal patients.
Source: PubMed