The impact of IGF-1R expression on the outcomes of patients with breast cancer: a meta-analysis

Abstract

Purpose: The value of insulin-like growth factor 1 receptor (IGF-1R) for predicting survival of patients with breast cancer remains controversial. The purpose of this study was to perform a meta-analysis of the published data to attempt to clarify the impact of IGF-1R.

Methods: Studies published between January 1, 1990 and October 1, 2014 were identified using an electronic search to aggregate the available survival results. Studies were included if they reported detecting IGF-1R expression in the primary breast cancer and analyzed patient survival data according to IGF-1R status. The principal outcome measures were hazard ratios (HRs) for survival of IGF-1R-positive patients. Combined HRs and 95% confidence intervals (CIs) were estimated using fixed- or random-effects models according to between-study heterogeneity.

Results: Ten studies, involving 5,406 patients, satisfied our inclusion criteria. Data from five studies provided the impact of IGF-1R on overall survival (OS), three studies the impact on breast cancer-specific survival (BCSS), and seven studies the impact on disease-free survival (DFS). The results of meta-analysis showed that for DFS, membranous IGF-1R positivity was not a significant predictor. The combined HR for OS/BCSS was 0.63 (95% CI: 0.42-0.95, P=0.03), indicating that membranous IGF-1R positivity was a significant predictor of better survival. IGF-1R cytoplasmic positivity was significantly associated with longer DFS and OS/BCSS (combined HR: 0.56, 95% CI: 0.35-0.89, P=0.01; combined HR: 0.55, 95% CI: 0.35-0.85, P=0.008, respectively). The results of subgroup analysis suggested that membranous IGF-1R positivity in hormone-receptor-positive breast cancer was correlated with favorable DFS (combined HR: 0.61, 95% CI: 0.41-0.92, P=0.02) and OS/BCSS (combined HR: 0.73, 95% CI: 0.57-0.93, P=0.01). Membranous IGF-1R positivity in triple-negative breast cancer predicted worse DFS (combined HR: 1.86, 95% CI: 1.03-3.34, P=0.04). Membranous IGF-1R positivity in Her-2-positive or ER (estrogen receptor)-negative breast cancer was not found to be a significant prognostic indicator.

Conclusion: The results of this meta-analysis suggest that IGF-1R expression has different prognostic values for patients with breast cancers of different molecular subtypes. It was a favorable prognostic indicator in unselected breast cancers and hormone-receptor-positive cancers, but indicated poor survival in triple-negative breast cancers.

Keywords: IGF-1R; breast cancer; disease-free survival; hazard ratio; meta-analysis; overall survival; prognosis.

Figure 1

Flow diagram of study selection. Abbreviations: N, number of studies; PCR, polymerase chain reaction.

Figure 2

Forest plot of hazard ratios (HRs) for disease-free survival (DFS) (A) and overall survival (OS)/breast cancer-specific survival (BCSS) (B) based on membranous insulin-like growth factor 1 receptor (IGF-1R) positivity, and DFS (C) and OS/BCSS (D) based on cytoplasmic IGF-1R positivity in the ten studies.

Figure 3

Forest plots of hazard ratios for disease-free survival (A) and overall survival (OS)/breast cancer-specific survival (BCSS) (B) of patients with hormone-receptor-positive breast cancers.

Figure 4

Forest plots of hazard ratios for disease-free survival (DFS) of patients with ER-negative breast cancers (A), for DFS of patients with triple-negative breast cancers (B), and for overall survival (OS)/breast cancer-specific survival (BCSS) of patients with Her-2-positive breast cancers (C).

Figure 5

Funnel plots for the disease-free survival (A) and overall survival (OS)/breast cancer-specific survival (BCSS) (B) of unspecified breast cancers. Abbreviations: SE, standard error; HR, hazard ratio.