Extended Adjuvant Therapy With Aromatase Inhibitors for Early Breast Cancer: A Meta-analysis of Randomized Controlled Trials

This meta-analysis aimed to assess the efficacy and toxicity of extended adjuvant aromatase inhibitors (AIs) in early breast cancer. Seven randomized clinical trials that involved 16,926 patients were selected for analysis. The results showed that extended AI therapy could significantly improve disease-free survival, especially for contralateral breast cancer recurrence. In addition, there were no significant differences between AIs and control for overall survival and serious adverse events. Background: Aromatase inhibitors (AIs) are widely used for early breast cancer, whereas the efficacy and safety of extended AI adjuvant therapy compared with shorter AI therapy, observation, or placebo remains controversial. We conducted a quantitative meta-analysis to summarize available randomized controlled trials (RCTs) regarding the efficacy and safety of extended AI therapy for early breast cancer. Materials and Methods: We systematically searched PubMed, EmBase, and the Cochrane library to select studies published through March 2018. Studies designed as RCTs and that investigated overall survival (OS) or disease-free survival (DFS) for extended AI and shorter AI therapy, observation, or placebo were included. Hazard ratio (HR) and relative risk (RR) with 95% confidence intervals (CIs) were employed to pool analysis according to data type. Results: We identified 7 RCTs that involved 16,926 patients with early breast cancer. The summary HRs indicated that extended treatment with AIs was not associated with OS (HR, 0.95; 95% CI, 0.82-1.10; P = .488), whereas it could significantly improve DFS as compared with shorter AI therapy, observation, or placebo (HR, 0.75; 95% CI, 0.66-0.86; P < .001). Treatment with extended AIs significantly reduced contralateral breast cancer recurrence (RR, 0.46; 95% CI, 0.34-0.64; P < .001), whereas it has no significant effect on distant metastatic recurrence (RR, 0.80; 95% CI, 0.64-1.00; P = .055), and locoregional recurrence (RR, 0.76; 95% CI, 0.53-1.08; P = .127). There were no significant differences between treatment with extended AIs and control for grade 3 or more adverse events. Conclusion: Extended AI therapy could significantly improve DFS, especially for contralateral breast cancer recurrence. There were no significant differences between treatment with AIs and control for OS, distant metastatic and locoregional recurrence, and serious adverse events. (C) 2019 Elsevier Inc. All rights reserved.