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Meta-Analysis
. 2016 Apr 13;11(4):e0152500.
doi: 10.1371/journal.pone.0152500. eCollection 2016.

The Prognostic Value of Tumor-Infiltrating Lymphocytes in Breast Cancer: A Systematic Review and Meta-Analysis

Yan Mao  1   2 , Qing Qu  3 , Xiaosong Chen  2 , Ou Huang  2 , Jiayi Wu  2 , Kunwei Shen  2
Affiliations
Meta-Analysis

The Prognostic Value of Tumor-Infiltrating Lymphocytes in Breast Cancer: A Systematic Review and Meta-Analysis

Yan Mao et al. PLoS One. .

Abstract

Background: The prognostic values of tumor-infiltrating lymphocytes (TILs) and TILs subsets in breast cancer (BC) are uncertain.

Methods: A systematic literature search (MEDLINE, Web of Science, EMBASE, and the Cochrane Library to August 2014) was conducted for studies which met the eligibility criteria. The primary clinical outcome was defined as disease-free survival (DFS), overall survival (OS), and BC-specific survival (BCSS). Random or fixed-effects model was adopted to estimate the summary hazard ratio (HR).

Results: Twenty-five published studies comprising 22,964 patients were reviewed. Pooled analysis indicated that TILs were not prognostic markers for DFS and OS in overall population, but related to improved DFS (HR, 0.82; 95% CI, 0.76-0.88) and OS (HR, 0.79; 95% CI, 0.71-0.87) in triple negative breast cancer (TNBC) patients. For TILs subsets, CD8+ lymphocytes were associated with improved DFS (HR, 0.69; 95% CI, 0.56-0.84) and BCSS (HR, 0.78; 95% CI, 0.71-0.86) in overall population, while FOXP3+ lymphocytes were associated with reduced DFS (HR, 1.47; 95% CI, 1.01-2.05) and OS (HR, 1.50; 95% CI, 1.15-1.97). In estrogen receptor (ER) negative patients, CD8+ lymphocytes was also related to better BCSS. In addition, the high density of CD20+, CD3+ or low level of PD-1+ or γδ T lymphocytes indicated increased OS in limited studies.

Conclusion: TILs and TILs subsets are promising prognostic biomarkers in breast cancer, especially in TNBC.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Flow chart of the studies included in the meta-analysis.
Fig 2
Fig 2. Forest plots of the random/fixed-effects meta-analysis for the efficacy of tumor-infiltrating lymphoctes for disease-free survival (DFS)(A) and overall survival (OS)(B) stratified by infiltration locations, including intratumoral site, stromal site, and both sites in breast cancer (BC) patients.
The horizontal bars indicate the 95% confidence inervals (CIs)The size of the square around eacheffect estimate indicates the weight of the individual study in the meta-analysis.
Fig 3
Fig 3. Forest plots of the random/fixed-effects meta-analysis for the efficacy of tumor-infiltrating lymphoctes for disease-free survival(DFS)(A,C,E) and overall survival (OS)(B,D,F) stratified by infiltration locations, including intratumoral site, stromal site, and both sites in ER+/HER2- (A,B), HER2+ (C,D), and triple-negative breast cancer (TNBC) (E,F) patients.
The horizontal bars indicate the 95% confidence intervals (CIs). The size of the square around eacheffect estimate indicates the weight of the individual study in the meta-analysis.
Fig 4
Fig 4. Forest plots of the random/fixed-effects meta-analysis for the efficacy of CD8+ (A,B,C) and FOXP3+ (D,E,F) lymphoctes for disease-free survival(DFS)(A,C), overall survival (OS)(B,D) and breast cancer specific survival (BCSS) stratified by infiltration locations, including intratumoral site, stromal site, and both sites in breast cancer patients.
The horizontal bars indicate the 95% confidence intervals (CIs). The size of the square around eacheffect estimate indicates the weight of the individual study in the meta-analysis.
Fig 5
Fig 5. Funnel plots of the relationship between the size of the effect in individual studies and the precision of the study estimate (lnHR, horizontal axis; s.e., vertical axis) for CD8+ cells.
See this image and copyright information in PMC

References

    1. Andre F, Dieci MV, Dubsky P, Sotiriou C, Curigliano G, Denkert C, et al. (2013) Molecular pathways: involvement of immune pathways in the therapeutic response and outcome in breast cancer. Clin Cancer Res 19: 28–33. 10.1158/1078-0432.CCR-11-2701 - DOI - PubMed
    1. Loi S, Sirtaine N, Piette F, Salgado R, Viale G, Van Eenoo F, et al. (2013) Prognostic and predictive value of tumor-infiltrating lymphocytes in a phase III randomized adjuvant breast cancer trial in node-positive breast cancer comparing the addition of docetaxel to doxorubicin with doxorubicin-based chemotherapy: BIG 02–98. J Clin Oncol 31: 860–867. 10.1200/JCO.2011.41.0902 - DOI - PubMed
    1. Mahmoud SM, Paish EC, Powe DG, Macmillan RD, Grainge MJ, Lee AH,et al. (2011) Tumor-infiltrating CD8+ lymphocytes predict clinical outcome in breast cancer. J Clin Oncol 29: 1949–1955. 10.1200/JCO.2010.30.5037 - DOI - PubMed
    1. Menard S, Tomasic G, Casalini P, Balsari A, Pilotti S, Cascinelli N,et al. (1997) Lymphoid infiltration as a prognostic variable for early-onset breast carcinomas. Clin Cancer Res 3: 817–819. - PubMed
    1. Mohammed ZM, Going JJ, Edwards J, Elsberger B, Doughty JC, McMillan DC. (2012) The relationship between components of tumour inflammatory cell infiltrate and clinicopathological factors and survival in patients with primary operable invasive ductal breast cancer. Br J Cancer 107: 864–873. 10.1038/bjc.2012.347 - DOI - PMC - PubMed

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