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

• Published in: Annals of oncology Vol. 23; no. 8; pp. 2027 - 2033
• Main Authors: Nuzzo, F., Gallo, C., Lastoria, S., Di Maio, M., Piccirillo, M.C., Gravina, A., Landi, G., Rossi, E., Pacilio, C., Labonia, V., Di Rella, F., Bartiromo, A., Buonfanti, G., De Feo, G., Esposito, G., D'Aniello, R., Maiolino, P., Signoriello, S., De Maio, E., Tinessa, V., Colantuoni, G., De Laurentiis, M., D'Aiuto, M., Di Bonito, M., Botti, G., Giordano, P., Daniele, G., Morabito, A., Normanno, N., de Matteis, A., Perrone, F.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01-08-2012; Oxford University Press
• Subjects: adjuvant hormonal treatment; Adult; Aged; Aged, 80 and over; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; body mass index; Bone Density - drug effects; Bone Density Conservation Agents - therapeutic use; bone mineral density; breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Chemotherapy, Adjuvant; Diphosphonates - therapeutic use; Estradiol - metabolism; Female; Gynecology. Andrology. Obstetrics; Humans; Imidazoles - therapeutic use; Letrozole; Mammary gland diseases; Medical sciences; Middle Aged; Neoplasm Staging; Nitriles - adverse effects; Nitriles - therapeutic use; Pharmacology. Drug treatments; phase 3 randomized trial; Tamoxifen - adverse effects; Tamoxifen - therapeutic use; Triazoles - adverse effects; Triazoles - therapeutic use; Tumors; Zoledronic Acid; bone mineral density; breast cancer; phase 3 randomized trial; body mass index; zoledronic acid; adjuvant hormonal treatment; Antineoplastic agent; Phase III trial; Antiosteoporotic; Breast disease; Hormone therapy; Azole derivatives; Antiestrogen; Adjuvant treatment; Antiresorptive agent; Diphosphonic acid derivatives; Early stage; Antihormone; Estrogen synthase; Bisphosphonates; Osteoarticular system; Body mass index; Randomization; Selective estrogen receptor modulator; Zoledronic acid; Non steroid compound; Aromatase inhibitor; Enzyme; Enzyme inhibitor; Breast cancer; Malignant tumor; Tamoxifene; Mammary gland diseases; Triazole derivatives; Bone mineral density; Bone; Letrozole; Cancer
• ISSN: 0923-7534; 1569-8041
• DOI: 10.1093/annonc/mdr600

To measure bone mineral density (BMD) reduction produced by letrozole as compared with tamoxifen and the benefit of the addition of zoledronic acid.
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.
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).
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.