The prognostic value of phosphorylated Akt in breast cancer: a systematic review

Abstract

The prognostic value of phosphorylated Akt (pAkt) overexpression in breast cancer has been investigated by many studies with inconsistent results. This systematic review was conducted to evaluate the association of pAkt overexpression with breast cancer prognosis in terms of overall survival and disease-free survival. Three electronic databases (PubMed, EMBASE and Chinese Biomedical Literature Database) were comprehensively searched. Hazard ratios (HRs) with 95% confidence intervals (CIs) from different studies were combined using the random-effects model. In total, 33 studies with 9,836 patients were included for final analysis. The summary HR for overall survival and disease-free survival was 1.52 (95% CI: 1.29-1.78) and 1.28 (95% CI: 1.13-1.45), respectively, indicating higher risk of death and disease recurrence associated with pAkt overexpression. The results were robust in sensitivity analyses by omitting one study each time and by using the fixed-effects model instead. Subgroup and meta-regression analyses did not show that the prognostic effect of pAkt overexpression would change materially with such factors as population, status of hormone receptors, hormonal or trastuzumab treatment given, analyzing method (univariate versus multivariate) and methodological quality of the original studies. In conclusion, the available evidence suggests that pAkt overexpression is an adverse prognostic factor for breast cancer.

Figure 1. Flow chart of study selection.

Figure 2. Meta-analysis of the association between pAkt overexpression and overall survival in breast cancer.

Results are presented as individual and pooled HRs with corresponding 95% CIs. HR > 1 means that overall survival of the patients with pAkt overexpression is worse than that of the pAkt-negative ones, while HR < 1 means the opposite.

Figure 3. Meta-analysis of the association between pAkt overexpression and disease-free survival in breast cancer.

Results are presented as individual and pooled HRs with corresponding 95% CIs. HR > 1 means that disease-free survival of the patients with pAkt overexpression is worse than that of the pAkt-negative ones, while HR < 1 means the opposite.

Figure 4. Funnel plots to examine the possibility of publication bias in the data for overall survival (A) and that for disease-free survival (B).

The standard error of log HR (S.E. of log HR) was plotted against log HR for each individual study as represented in a circle. Egger's tests showed that the funnel plots were asymmetric (P < 0.001 for Figure 4(A); P = 0.002 for Figure 4(B)), which could be due to potential publication bias among other reasons.