Worse outcome in breast cancer with higher tumor-infiltrating FOXP3+ Tregs : a systematic review and meta-analysis

Jiafeng Shou, Zhigang Zhang, Yucheng Lai, Zhigang Chen, Jian Huang, Jiafeng Shou, Zhigang Zhang, Yucheng Lai, Zhigang Chen, Jian Huang

Abstract

Background: 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. However, the research on the prognostic significance of tumor-infiltrating FOXP3+ Tregs in breast cancer is still limited and the results are controversial.

Methods: We 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.

Result: A 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).

Conclusion: The 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.

Keywords: Breast cancer; FOXP3; Prognosis; TIL.

Figures

Fig. 1
Fig. 1
Flow diagram showing the study selection procedure
Fig. 2
Fig. 2
Forest plot of the hazard ratio (HR) for the association of FOXP3+ level with overall survival (OS) in breast cancer patients
Fig. 3
Fig. 3
Forest plot of the hazard ratio (HR) for the association of FOXP3+ level with relapse free survival (RFS) in breast cancer patients
Fig. 4
Fig. 4
Forest plot assessing the FOXP3+ TILs and clinicopathological features such as ER status (a), PR status (b), c-erbB-2 status (c), tumor category (d), lymph node category (e)
Fig. 5
Fig. 5
Begg’s test results of the OS (a) and RFS (b)
Fig. 6
Fig. 6
Begg’s test assessing the FOXP3+ TILs and clinicopathological features such as ER status (a), PR status (b), c-erbB-2 status (c), tumor category (d), lymph node category (e)

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