title: The protective effect of zoledronic acid on bone loss in postmenopausal women with early breast cancer treated with sequential tamoxifen and letrozole: a prospective, randomized, phase II trial.
abstract: OBJECTIVE
  This study reports the efficacy and safety of zoledronic acid (ZOL) in preventing bone loss in postmenopausal patients receiving an aromatase inhibitor (AI) following tamoxifen.
  
  
  METHODS
  Postmenopausal patients with stage I-III hormone receptor-positive breast cancer who received tamoxifen for 2.5-3 years were randomized to receive letrozole (2.5 mg/day) with (n = 47) or without (n = 43) ZOL (4 mg i.v. every 6 months) for 2 years. The primary endpoint was percent change from baseline in lumbar spine (LS) bone mineral density (BMD) up to 60 months.
  
  
  RESULTS
  Ninety patients (86 evaluable) with a median age of 59 years (42.9-83.6), 50/86 of whom had previously been treated with chemotherapy, were followed for a median time of 41.4 months. While the control group showed a significant decrease in LS T-score (p = 0.0005), the ZOL group presented an increase over time (p = 0.0143). Change over time in LS T-score was significantly different between groups, favoring ZOL (p < 0.0001 at 24 and 48 months). No fractures, renal dysfunction or osteonecrosis of the jaw were reported. The toxicity profile was similar to those previously reported for each drug.
  
  
  CONCLUSIONS
  The addition of ZOL to letrozole was safe and efficacious in maintaining LS BMD in postmenopausal patients with hormone receptor-positive breast cancer and who were receiving letrozole following 2.5-3 years of tamoxifen.
authors.affiliation: Department of Oncology, Tel Aviv Sourasky Medical Center, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. safrat@bezeqint.net
authors.forename: Tamar
authors.initials: T
authors.lastname: Safra
authors.forename: Rinat
authors.initials: R
authors.lastname: Bernstein-Molho
authors.forename: Julia
authors.initials: J
authors.lastname: Greenberg
authors.forename: Sharon
authors.initials: S
authors.lastname: Pelles-Avraham
authors.forename: Irina
authors.initials: I
authors.lastname: Stephansky
authors.forename: David
authors.initials: D
authors.lastname: Sarid
authors.forename: Moshe J
authors.initials: MJ
authors.lastname: Inbar
authors.forename: Salomon M
authors.initials: SM
authors.lastname: Stemmer
authors.forename: David B
authors.initials: DB
authors.lastname: Geffen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D047072:Aromatase Inhibitors / Q000627:therapeutic use; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004164:Diphosphonates / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D000077289:Letrozole; D008875:Middle Aged; D009367:Neoplasm Staging / Q000379:methods; D009570:Nitriles / Q000627:therapeutic use*; D015663:Osteoporosis, Postmenopausal / Q000517:prevention & control*; D011446:Prospective Studies; D013629:Tamoxifen / Q000627:therapeutic use*; D014230:Triazoles / Q000627:therapeutic use*; D000077211:Zoledronic Acid
chemical_list: D000970:Antineoplastic Agents; D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D009570:Nitriles; D014230:Triazoles; D013629:Tamoxifen; D000077211:Zoledronic Acid; D000077289:Letrozole