title: The efficacy of zoledronic acid in breast cancer adjuvant therapy: a meta-analysis of randomised controlled trials.
abstract: BACKGROUND
  The effect of zoledronic acid in breast cancer adjuvant therapy concerning improvement of patient survival has yet to be confirmed. We performed a meta-analysis of published and unpublished randomised controlled trials with the aim of accurate evaluation between clinical outcome and the association of the addition of zoledronic acid to adjuvant therapy.
  
  
  METHODS
  We searched PubMed (from 1966 to present) and online abstracts from the proceeding Annual Meetings of the American Society of Clinical Oncology (ASCO) (years 1992-2010) and online abstracts from San Antonio Breast Cancer Symposium (years 2004-2010). A total of five eligible studies including 3676 subjects and 3678 controls met our search criteria and were evaluated. Random and fixed-effects meta-analytical models were used where indicated, and between-study heterogeneity was assessed. The primary study end-points were the disease free survival (DFS). Secondary end-points were overall survival (OS), distant or loco-regional recurrence free survival and bone metastasis free survival.
  
  
  RESULTS
  Compared with the control arm, adjuvant breast cancer treatment with zoledronic acid did not significantly improve overall survival, disease free survival, bone metastasis free survival, distant and locoregional recurrence free survival. However, in the postmenopausal subgroup, the addition of zoledronic acid to standard therapy could significantly improve DFS (relative risk (RR) = 0.763, 95% confidence interval (CI) 0.658-0.884, p < 0.001) and reduce the risk of distant (RR = 0.744, 95%CI 0.611-0.906, p = 0.003) and locoregional recurrence (RR = 0.508, 95%CI 0.340-0.760, p = 0.001).
  
  
  CONCLUSIONS
  Adjuvant zoledronic acid did not significantly improve the prognosis of breast cancer patients. Due to the highly variable definitions of menopause utilised in different studies, we hypothesise that zoledronic acid may have a potential effect on postmenopausal patients. Additional studies are needed to evaluate the value of adjuvant treatment of zoledronic acid in premenopausal counterparts, differing disease stages and various pathological types of breast cancer.
authors.affiliation: Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Yan
authors.forename: Wenjin
authors.initials: W
authors.lastname: Yin
authors.forename: Qiong
authors.initials: Q
authors.lastname: Zhou
authors.forename: Liheng
authors.initials: L
authors.lastname: Zhou
authors.forename: Yiwei
authors.initials: Y
authors.lastname: Jiang
authors.forename: Yueyao
authors.initials: Y
authors.lastname: Du
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Shao
authors.forename: Jinsong
authors.initials: J
authors.lastname: Lu
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D050071:Bone Density Conservation Agents / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality; D017024:Chemotherapy, Adjuvant; D004164:Diphosphonates / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D009364:Neoplasm Recurrence, Local; D016032:Randomized Controlled Trials as Topic; D016019:Survival Analysis; D000077211:Zoledronic Acid
chemical_list: D000970:Antineoplastic Agents; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid