Bisphosphonates in the adjuvant setting of breast cancer therapy--effect on survival: a systematic review and meta-analysis

PLoS One. 2013 Aug 26;8(8):e70044. doi: 10.1371/journal.pone.0070044. eCollection 2013.


Background: The role of bisphosphonates (BP) in early breast cancer (BC) has been considered controversial. We performed a meta-analysis of all randomized controlled trials (RCTs) that appraised the effects of BP on survival in early BC.

Methods: RCTs were identified by searching the Cochrane Library, MEDLINE databases and conference proceedings. Hazard ratios (HRs) of overall survival (OS), disease-free survival (DFS) and relative risks of adverse events were estimated and pooled.

Results: Thirteen trials met the inclusion criteria, evaluating a total of 15,762 patients. Meta-analysis of ten trials which reported OS revealed no statistically significant benefit in OS for BP (HR 0.89, 95% CI = 0.79 to 1.01). Meta-analysis of nine trials which reported the DFS revealed no benefit in DFS (HR 0.95 (0.81-1.12)). Meta-analysis upon menopausal status showed a statistically significant better DFS in the BP-treated patients (HR 0.81(0.69-0.95)). In meta-regression, chemotherapy was negatively associated with HR of survival.

Conclusions: Our meta-analysis indicates a positive effect for adjuvant BP on survival only in postmenopausal patients. Meta-regression demonstrated a negative association between chemotherapy use BP effect on survival. Further large scale RCTs are warranted to unravel the specific subgroups that would benefit from the addition of BP in the adjuvant setting.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Antineoplastic Agents / therapeutic use
  • Bone Density Conservation Agents / therapeutic use
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / mortality*
  • Chemotherapy, Adjuvant / methods*
  • Clodronic Acid / therapeutic use
  • Diphosphonates / therapeutic use*
  • Disease-Free Survival
  • Etidronic Acid / analogs & derivatives
  • Etidronic Acid / therapeutic use
  • Female
  • Humans
  • Ibandronic Acid
  • Pamidronate
  • Proportional Hazards Models
  • Randomized Controlled Trials as Topic
  • Research Design
  • Risedronic Acid
  • Risk
  • Treatment Outcome


  • Antineoplastic Agents
  • Bone Density Conservation Agents
  • Diphosphonates
  • Clodronic Acid
  • Risedronic Acid
  • Etidronic Acid
  • Pamidronate
  • Ibandronic Acid

Grant support

The authors have no external support or funding to report.