Regulatory T cells are an important prognostic factor in breast cancer: a systematic review and meta-analysis.

The clinical relevance of regulatory T cell (Treg) infiltration in breast cancer (BC) remains controversial, and no recent meta-analysis has been published on this subject. Our aim was to identify the precise relationship between Tregs and the prognosis and clinic-pathological features of BC. Eligible articles were identified with a MEDLINE database search over a period up to March 2015. Our meta-analysis was performed using STATA software 11.0 and Review Manager 5.3. The correlations between Treg infiltration and clinico-pathological features and BC prognosis were analyzed. Subgroup and sensitivity analyses, as well as meta-regression, were conducted. Eighteen published studies (including 8,562 patients) were eligible. Overall survival (OS) and disease-, recurrence-, and progression-free survival (DFS/RFS/PFS) were correlated with Treg infiltration (OR=2.03 (95% CI, 1.40-2.95; P=0.000) and 1.48 (95% CI, 1.00-2.19; P=0.050), respectively), including 3-, 5-, and 10-year mortality rates. In addition, low Treg infiltration was present in estrogen receptor (ER)-positive tumors (P=0.000), progesterone receptor (PR)-positive tumors (P=0.003), Her2-negative tumors (P=0.000) and histological grade I/II tumors (P=0.001). No publication bias was observed with the exception of OS. Subgroup analysis suggested that the mortality rate of the high Treg infiltration subgroup was increased compared with the low Treg infiltration subgroup among ER-positive patients. Treg infiltration indicated a poorer prognosis for BC and is related to ER, PR, and Her2 status and histological grade. Thus, Treg infiltration could help predict outcomes and guide clinical therapy.