Bone effect of adjuvant tamoxifen, letrozole or letrozole plus zoledronic acid in early-stage breast cancer: the randomized phase 3 HOBOE study.

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.

• Authors: 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
• Journal: Annals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 23 Issue 8 Pg. 2027-2033 (Aug 2012) ISSN: 1569-8041 [Electronic] England
• PMID: 22412041 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Bone Density Conservation Agents
• Diphosphonates
• Imidazoles
• Nitriles
• Triazoles
• Tamoxifen
• Estradiol
• Zoledronic Acid
• Letrozole

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Bone Density (drug effects)
• Bone Density Conservation Agents (therapeutic use)
• Breast Neoplasms (drug therapy, metabolism, pathology)
• Chemotherapy, Adjuvant
• Diphosphonates (therapeutic use)
• Estradiol (metabolism)
• Female
• Humans
• Imidazoles (therapeutic use)
• Letrozole
• Middle Aged
• Neoplasm Staging
• Nitriles (adverse effects, therapeutic use)
• Tamoxifen (adverse effects, therapeutic use)
• Triazoles (adverse effects, therapeutic use)
• Zoledronic Acid