Abstract
BackgroundForkhead box P3(FOXP3) is known as the optimum maker for regulatory T cells(Tregs), which are conventionally thought to induce immune tolerance to disturb the antitumor immunity. However, the research on the prognostic significance of tumor-infiltrating FOXP3+ Tregs in breast cancer is still limited and the results are controversial.MethodsWe searched for studies in PubMed, EMBASE and Web of Science prior to January 2015. The correlation between FOXP3+ tumor-infiltrating lymphocytes(TILs) and breast cancer prognosis was analyzed. The meta-analysis was performed using STATA 11.0. Pooled hazard ratios (HRs) with 95 % confidence intervals (CIs) were used to estimate the degree of the association between FOXP3+ TILs and prognosis of breast cancers, while relative ratios (RRs) were used to evaluate the relationship between FOXP3+ TILs and clinicopathological features of breast cancers.ResultA total of 15 studies comprising 8666 breast cancer patients met the inclusion criteria. Our results showed that higher FOXP3+ TILs level was significantly associated with poor prognosis in terms of overall survival (OS) (pooled HR:1.60, 95 % CI:1.06–2.42; P < 0.05). We found that breast cancer with higher FOXP3+ TILs level was positively correlated with c-erbB-2 positive status (pooled RR:1.52, 95 % CI:1.32–1.75; P < 0.05), lymph node positive status(pooled RR:1.17, 95 % CI:1.04–1.32; P < 0.05) while there was a negative association with ER positive status(pooled RR:0.65, 95 % CI:0.56–0.76; P < 0.05) and PR positive status(pooled RR:0.66, 95 % CI:0.51–0.87; P < 0.05).ConclusionThe present results of meta-analysis showed that higher FOXP3+ TILs level in patients with breast cancer led to poor overall survival (OS) and was significantly associated with c-erbB-2 status, lymph node status, ER status and PR status. FOXP3+ TILs level is a promising prognostic factor in breast cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2732-0) contains supplementary material, which is available to authorized users.
Highlights
Forkhead box P3(FOXP3) is known as the optimum maker for regulatory T cells(Tregs), which are conventionally thought to induce immune tolerance to disturb the antitumor immunity
The present results of meta-analysis showed that higher FOXP3+ tumor-infiltrating lymphocytes (TILs) level in patients with breast cancer led to poor overall survival (OS) and was significantly associated with c-erbB-2 status, lymph node status, ER status and PR status
Selection criteria The studies included in our meta-analysis should meet following criteria: [1] the study must be conducted on the human beings; [2] the study must assess the association between FOXP3+ TILs level and the prognosis of breast cancer; [3] The count of FOXP3+ TIL include either tumor bed or tumor peripheral lymphocytes [4] the study must contain sufficient published data to determine an estimate of hazard ratio(HR) and a 95 % confidence interval(95 % Confidence interval (CI)); [5] original research article must be published in English
Summary
Forkhead box P3(FOXP3) is known as the optimum maker for regulatory T cells(Tregs), which are conventionally thought to induce immune tolerance to disturb the antitumor immunity. In most cancers, including breast cancer [2,3,4], infiltrating of FOXP3+ regulatory TILs have been reported to be associated with worse clinical outcome. Studies to confirm the clinical significance of FOXP3+ TILs in breast cancer are still insufficient and the prognostic value still lacks assessment, especially in different molecule types of breast cancer. We find it necessary to further assess the association between tumor-infiltrating FOXP3+ Tregs and prognosis of breast cancer by conducting a meta-analysis with a large sample size (N = 8666). The relationship between FOXP3+ TILs and several clinicopathological features of breast cancer was evaluated
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