title: Final 5-year results of Z-FAST trial: adjuvant zoledronic acid maintains bone mass in postmenopausal breast cancer patients receiving letrozole.
abstract: BACKGROUND
  Postmenopausal breast cancer (BC) patients receiving adjuvant aromatase inhibitor therapy are at risk of progressive bone loss and fractures. Zoledronic acid inhibits osteoclastic bone resorption, is effective in maintaining bone health, and may therefore be beneficial in this setting.
  
  
  METHODS
  Overall, 602 postmenopausal women with early, hormone receptor-positive BC receiving adjuvant letrozole were randomized (301 each group) to receive upfront or delayed-start zoledronic acid (4 mg intravenously every 6 months) for 5 years. The primary endpoint was the change in lumbar spine (LS) bone mineral density (BMD) at month 12. Secondary endpoints included changes in LS BMD, total hip BMD, and bone turnover markers at 2, 3, and 5 years; fracture incidence at 3 years; and time to disease recurrence.
  
  
  RESULTS
  At month 61, the adjusted mean difference in LS and total hip BMDs between the upfront and delayed groups was 8.9% and 6.7%, respectively (P < .0001, for both). Approximately 25% of delayed patients received zoledronic acid by month 61. Only 1 patient experienced grade 4 renal dysfunction; no confirmed cases of osteonecrosis of the jaw were reported. Fracture rates (upfront, 28 [9.3%]; delayed, 33 [11%]; P = .3803) and Kaplan-Meier disease recurrence rates (upfront, 9.8 [95% confidence interval (CI), 6.0-10.3]; delayed, 10.5 [95% CI, 6.6-14.4]; P = .6283) were similar at month 61.
  
  
  CONCLUSIONS
  Upfront zoledronic acid seems to be the preferred treatment strategy versus delayed administration, as it significantly and progressively increases BMD in postmenopausal women with early BC receiving letrozole for 5 years, and long-term coadministration of letrozole and zoledronic acid is well tolerated.
authors: Magee-Womens Hospital, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA. brufskyam@upmc.edu
authors: Adam M
authors: AM
authors: Brufsky
authors: W Graydon
authors: WG
authors: Harker
authors: J Thaddeus
authors: JT
authors: Beck
authors: Linda
authors: L
authors: Bosserman
authors: Charles
authors: C
authors: Vogel
authors: Christopher
authors: C
authors: Seidler
authors: Lixian
authors: L
authors: Jin
authors: Ghulam
authors: G
authors: Warsi
authors: Eliza
authors: E
authors: Argonza-Aviles
authors: John
authors: J
authors: Hohneker
authors: Solveig G
authors: SG
authors: Ericson
authors: Edith A
authors: EA
authors: Perez
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001842:Bone and Bones / Q000187:drug effects* / Q000473:pathology; D001943:Breast Neoplasms / Q000150:complications / Q000188:drug therapy*; D002277:Carcinoma / Q000150:complications / Q000188:drug therapy*; D017024:Chemotherapy, Adjuvant; D004164:Diphosphonates / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D000077289:Letrozole; D008875:Middle Aged; D009570:Nitriles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D009929:Organ Size / Q000187:drug effects; D015663:Osteoporosis, Postmenopausal / Q000139:chemically induced / Q000150:complications / Q000453:epidemiology / Q000517:prevention & control*; D017698:Postmenopause / Q000187:drug effects; D014230:Triazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000077211:Zoledronic Acid
chemical_list: D000970:Antineoplastic Agents; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D009570:Nitriles; D014230:Triazoles; D000077211:Zoledronic Acid; D000077289:Letrozole