title: 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.
  
  
  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.affiliation: Medical Oncology, Department of Senology, National Cancer Institute, Napoli.
authors.forename: F
authors.initials: F
authors.lastname: Nuzzo
authors.affiliation: Medical Statistics, Department of Medicine and Public Health, Second University, Napoli.
authors.forename: C
authors.initials: C
authors.lastname: Gallo
authors.affiliation: Nuclear Medicine and Metabolic Therapy, Department of Imaging, National Cancer Institute, Napoli.
authors.forename: S
authors.initials: S
authors.lastname: Lastoria
authors.affiliation: Clinical Trials Unit, Department of Research, National Cancer Institute, Napoli.
authors.forename: M
authors.initials: M
authors.lastname: Di Maio
authors.affiliation: Clinical Trials Unit, Department of Research, National Cancer Institute, Napoli.
authors.forename: M C
authors.initials: MC
authors.lastname: Piccirillo
authors.affiliation: Medical Oncology, Department of Senology, National Cancer Institute, Napoli.
authors.forename: A
authors.initials: A
authors.lastname: Gravina
authors.affiliation: Medical Oncology, Department of Senology, National Cancer Institute, Napoli.
authors.forename: G
authors.initials: G
authors.lastname: Landi
authors.affiliation: Medical Oncology, Department of Senology, National Cancer Institute, Napoli; Division of Medical Oncology, Department of Oncohematology, S. Giuseppe Moscati Hospital, Avellino.
authors.forename: E
authors.initials: E
authors.lastname: Rossi
authors.affiliation: Medical Oncology, Department of Senology, National Cancer Institute, Napoli.
authors.forename: C
authors.initials: C
authors.lastname: Pacilio
authors.affiliation: Medical Oncology, Department of Senology, National Cancer Institute, Napoli.
authors.forename: V
authors.initials: V
authors.lastname: Labonia
authors.affiliation: Medical Oncology, Department of Senology, National Cancer Institute, Napoli.
authors.forename: F
authors.initials: F
authors.lastname: Di Rella
authors.affiliation: Nuclear Medicine and Metabolic Therapy, Department of Imaging, National Cancer Institute, Napoli.
authors.forename: A
authors.initials: A
authors.lastname: Bartiromo
authors.affiliation: Medical Oncology, Department of Senology, National Cancer Institute, Napoli.
authors.forename: G
authors.initials: G
authors.lastname: Buonfanti
authors.affiliation: Clinical Trials Unit, Department of Research, National Cancer Institute, Napoli.
authors.forename: G
authors.initials: G
authors.lastname: De Feo
authors.affiliation: Laboratory Medicine, Department of Pathology and Laboratory Diagnostics, National Cancer Institute, Napoli.
authors.forename: G
authors.initials: G
authors.lastname: Esposito
authors.affiliation: Department of Pharmacy, National Cancer Institute, Napoli.
authors.forename: R
authors.initials: R
authors.lastname: D'Aniello
authors.affiliation: Department of Pharmacy, National Cancer Institute, Napoli.
authors.forename: P
authors.initials: P
authors.lastname: Maiolino
authors.affiliation: Medical Statistics, Department of Medicine and Public Health, Second University, Napoli.
authors.forename: S
authors.initials: S
authors.lastname: Signoriello
authors.affiliation: Clinical Trials Unit, Department of Research, National Cancer Institute, Napoli.
authors.forename: E
authors.initials: E
authors.lastname: De Maio
authors.affiliation: Division of Medical Oncology, Department of Oncology, Rummo Hospital, Benevento.
authors.forename: V
authors.initials: V
authors.lastname: Tinessa
authors.affiliation: Division of Medical Oncology, Department of Oncohematology, S. Giuseppe Moscati Hospital, Avellino.
authors.forename: G
authors.initials: G
authors.lastname: Colantuoni
authors.affiliation: Medical Oncology, Department of Senology, National Cancer Institute, Napoli.
authors.forename: M
authors.initials: M
authors.lastname: De Laurentiis
authors.affiliation: Division of Surgical Oncology, Department of Senology, National Cancer Institute, Napoli.
authors.forename: M
authors.initials: M
authors.lastname: D'Aiuto
authors.affiliation: Pathology, Department of Pathology and Laboratory Diagnostics, National Cancer Institute, Napoli.
authors.forename: M
authors.initials: M
authors.lastname: Di Bonito
authors.affiliation: Pathology, Department of Pathology and Laboratory Diagnostics, National Cancer Institute, Napoli.
authors.forename: G
authors.initials: G
authors.lastname: Botti
authors.affiliation: Clinical Trials Unit, Department of Research, National Cancer Institute, Napoli.
authors.forename: P
authors.initials: P
authors.lastname: Giordano
authors.affiliation: Clinical Trials Unit, Department of Research, National Cancer Institute, Napoli.
authors.forename: G
authors.initials: G
authors.lastname: Daniele
authors.affiliation: Clinical Trials Unit, Department of Research, National Cancer Institute, Napoli.
authors.forename: A
authors.initials: A
authors.lastname: Morabito
authors.affiliation: Cellular Biology and Biotherapy, Department of Research, National Cancer Institute, Napoli, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Normanno
authors.affiliation: Medical Oncology, Department of Senology, National Cancer Institute, Napoli.
authors.forename: A
authors.initials: A
authors.lastname: de Matteis
authors.affiliation: Clinical Trials Unit, Department of Research, National Cancer Institute, Napoli. Electronic address: francesco.perrone@usc-intnapoli.net.
authors.forename: F
authors.initials: F
authors.lastname: Perrone
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D004164:Diphosphonates / Q000627:therapeutic use*; D004958:Estradiol / Q000378:metabolism; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D000077289:Letrozole; D008875:Middle Aged; D009367:Neoplasm Staging; D009570:Nitriles / Q000009:adverse effects / Q000627:therapeutic use; D013629:Tamoxifen / Q000009:adverse effects / Q000627:therapeutic use*; D014230:Triazoles / Q000009:adverse effects / Q000627:therapeutic use; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D009570:Nitriles; D014230:Triazoles; D013629:Tamoxifen; D004958:Estradiol; D000077211:Zoledronic Acid; D000077289:Letrozole