Open AccessBisphosphonates in the Adjuvant Setting of Breast Cancer Therapy—Effect on Survival: A Systematic Review and Meta-Analysis
Author(s) -
Irit BenAharon,
Liat Vidal,
Shulamith Rizel,
Rinat Yerushalmi,
Ofer Shpilberg,
Aarón Sulkes,
Salomon M. Stemmer
Publication year - 2013
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0070044
Subject(s) - medicine , meta analysis , cochrane library , breast cancer , hazard ratio , oncology , randomized controlled trial , adverse effect , adjuvant therapy , medline , proportional hazards model , cancer , confidence interval , political science , law
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.