Limits...
The value of tumor infiltrating lymphocytes (TILs) for predicting response to neoadjuvant chemotherapy in breast cancer: a systematic review and meta-analysis.

Mao Y, Qu Q, Zhang Y, Liu J, Chen X, Shen K - PLoS ONE (2014)

Bottom Line: Random or fixed effect models were adopted to estimate the summary odds ratio (OR).Heterogeneity and sensitivity analyses were performed to explore heterogeneity among studies and to assess the effects of study quality.Only FOXP3+ lymphocytes in post-NAC breast tissue were a predictive marker for low pCR rate in univariate (OR = 0.41, 95% CI: 0.21-0.80) and multivariate (OR = 0.36, 95% CI: 0.13-0.95) analysis.

View Article: PubMed Central - PubMed

Affiliation: Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

ABSTRACT

Background: We carried out a systematic review and meta-analysis to evaluate the predictive roles of tumor infiltrating lymphocytes (TILs) in response to neoadjuvant chemotherapy (NAC) in breast cancer.

Method: A PubMed and Web of Science literature search was designed. Random or fixed effect models were adopted to estimate the summary odds ratio (OR). Heterogeneity and sensitivity analyses were performed to explore heterogeneity among studies and to assess the effects of study quality. Publication bias was evaluated using a funnel plot, Egger's test and Begg's test. We included studies where the predictive significance of TILs, and/or TILs subset on the pathologic complete response (pCR) were determined in NAC of breast cancer.

Results: A total of 13 published studies (including 3251 patients) were eligible. In pooled analysis, the detection of higher TILs numbers in pre-treatment biopsy was correlated with better pCR to NAC (OR = 3.93, 95% CI, 3.26-4.73). Moreover, TILs predicted higher pCR rates in triple negative (OR = 2.49, 95% CI: 1.61-3.83), HER2 positive (OR = 5.05, 95% CI: 2.86-8.92) breast cancer, but not in estrogen receptor (ER) positive (OR = 6.21, 95%CI: 0.86-45.15) patients. In multivariate analysis, TILs were still an independent marker for high pCR rate (OR = 1.41, 95% CI: 1.19-1.66). For TILs subset, higher levels of CD8+ and FOXP3+ T-lymphocytes in pre-treatment biopsy respectively predicted better pathological response to NAC (OR = 6.44, 95% CI: 2.52-16.46; OR = 2.94, 95% CI: 1.05-8.26). Only FOXP3+ lymphocytes in post-NAC breast tissue were a predictive marker for low pCR rate in univariate (OR = 0.41, 95% CI: 0.21-0.80) and multivariate (OR = 0.36, 95% CI: 0.13-0.95) analysis.

Conclusion: Higher TILs levels in pre-treatment biopsy indicated higher pCR rates for NAC. TILs subset played different roles in predicting response to NAC.

Show MeSH

Related in: MedlinePlus

Forest plots from the fixed- or random-effect meta-analysis of the efficacy of TILs subset on NAC response in pre-treatment biopsy (A, B).The width of horizontal line represents 95% CI of the individual studies, and the grey boxes represent the weight of each study. The diamond represents the overall summary estimate. The unbroken vertical line was set at the  value (HR = 1.0).
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4264870&req=5

pone-0115103-g005: Forest plots from the fixed- or random-effect meta-analysis of the efficacy of TILs subset on NAC response in pre-treatment biopsy (A, B).The width of horizontal line represents 95% CI of the individual studies, and the grey boxes represent the weight of each study. The diamond represents the overall summary estimate. The unbroken vertical line was set at the value (HR = 1.0).

Mentions: The most commonly tested markers for TILs subset tested in breast cancer are CD3+, CD4+, CD8+ and FOXP3+. Seven studies [24], [25], [27], [28], [30], [32], [42] were pooled for analysis of the association between T lymphocytes subsets and the pCR rate in univariate way. Five studies reported which subset were present in pre-treatment biopsy, and the pooled analysis showed that higher level of CD8+ (OR = 6.44, 95% CI, 2.52–16.46, P = 0.000; Fig. 5A) and FOXP3+ (OR = 2.94, 95% CI, 1.05–8.26, P = 0.041; Fig. 5B) lymphocytes indicated a better pathologic response to NAC, while the presence of CD3+ lymphocytes had no predictive values (OR = 1.56, 95% CI, 0.99–2.45, P = 0.055; Fig. 5B). Although CD4+ infiltrating lymphocytes also indicated a good response to NAC in pre-treatment biopsy (OR = 7.33, 95% CI, 2.03–26.40, P = 0.002; Fig. 5B), there is only one study tested this relationship. More prospective studies are needed to address this issue. Three studies [24], [27], [28] reported the presence of TILs subset in post-treatment breast tissue and indicated that higher levels of FOXP3+ lymphocytes infiltration after treatment indicated lower response to NAC (OR = 0.41, 95% CI, 0.21–0.80, P = 0.009; Fig. 6). Since there was not enough data available concerning the correlation of TILs subset in different locations and subtypes with NAC response, we were unable to perform further analysis.


The value of tumor infiltrating lymphocytes (TILs) for predicting response to neoadjuvant chemotherapy in breast cancer: a systematic review and meta-analysis.

Mao Y, Qu Q, Zhang Y, Liu J, Chen X, Shen K - PLoS ONE (2014)

Forest plots from the fixed- or random-effect meta-analysis of the efficacy of TILs subset on NAC response in pre-treatment biopsy (A, B).The width of horizontal line represents 95% CI of the individual studies, and the grey boxes represent the weight of each study. The diamond represents the overall summary estimate. The unbroken vertical line was set at the  value (HR = 1.0).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4264870&req=5

pone-0115103-g005: Forest plots from the fixed- or random-effect meta-analysis of the efficacy of TILs subset on NAC response in pre-treatment biopsy (A, B).The width of horizontal line represents 95% CI of the individual studies, and the grey boxes represent the weight of each study. The diamond represents the overall summary estimate. The unbroken vertical line was set at the value (HR = 1.0).
Mentions: The most commonly tested markers for TILs subset tested in breast cancer are CD3+, CD4+, CD8+ and FOXP3+. Seven studies [24], [25], [27], [28], [30], [32], [42] were pooled for analysis of the association between T lymphocytes subsets and the pCR rate in univariate way. Five studies reported which subset were present in pre-treatment biopsy, and the pooled analysis showed that higher level of CD8+ (OR = 6.44, 95% CI, 2.52–16.46, P = 0.000; Fig. 5A) and FOXP3+ (OR = 2.94, 95% CI, 1.05–8.26, P = 0.041; Fig. 5B) lymphocytes indicated a better pathologic response to NAC, while the presence of CD3+ lymphocytes had no predictive values (OR = 1.56, 95% CI, 0.99–2.45, P = 0.055; Fig. 5B). Although CD4+ infiltrating lymphocytes also indicated a good response to NAC in pre-treatment biopsy (OR = 7.33, 95% CI, 2.03–26.40, P = 0.002; Fig. 5B), there is only one study tested this relationship. More prospective studies are needed to address this issue. Three studies [24], [27], [28] reported the presence of TILs subset in post-treatment breast tissue and indicated that higher levels of FOXP3+ lymphocytes infiltration after treatment indicated lower response to NAC (OR = 0.41, 95% CI, 0.21–0.80, P = 0.009; Fig. 6). Since there was not enough data available concerning the correlation of TILs subset in different locations and subtypes with NAC response, we were unable to perform further analysis.

Bottom Line: Random or fixed effect models were adopted to estimate the summary odds ratio (OR).Heterogeneity and sensitivity analyses were performed to explore heterogeneity among studies and to assess the effects of study quality.Only FOXP3+ lymphocytes in post-NAC breast tissue were a predictive marker for low pCR rate in univariate (OR = 0.41, 95% CI: 0.21-0.80) and multivariate (OR = 0.36, 95% CI: 0.13-0.95) analysis.

View Article: PubMed Central - PubMed

Affiliation: Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

ABSTRACT

Background: We carried out a systematic review and meta-analysis to evaluate the predictive roles of tumor infiltrating lymphocytes (TILs) in response to neoadjuvant chemotherapy (NAC) in breast cancer.

Method: A PubMed and Web of Science literature search was designed. Random or fixed effect models were adopted to estimate the summary odds ratio (OR). Heterogeneity and sensitivity analyses were performed to explore heterogeneity among studies and to assess the effects of study quality. Publication bias was evaluated using a funnel plot, Egger's test and Begg's test. We included studies where the predictive significance of TILs, and/or TILs subset on the pathologic complete response (pCR) were determined in NAC of breast cancer.

Results: A total of 13 published studies (including 3251 patients) were eligible. In pooled analysis, the detection of higher TILs numbers in pre-treatment biopsy was correlated with better pCR to NAC (OR = 3.93, 95% CI, 3.26-4.73). Moreover, TILs predicted higher pCR rates in triple negative (OR = 2.49, 95% CI: 1.61-3.83), HER2 positive (OR = 5.05, 95% CI: 2.86-8.92) breast cancer, but not in estrogen receptor (ER) positive (OR = 6.21, 95%CI: 0.86-45.15) patients. In multivariate analysis, TILs were still an independent marker for high pCR rate (OR = 1.41, 95% CI: 1.19-1.66). For TILs subset, higher levels of CD8+ and FOXP3+ T-lymphocytes in pre-treatment biopsy respectively predicted better pathological response to NAC (OR = 6.44, 95% CI: 2.52-16.46; OR = 2.94, 95% CI: 1.05-8.26). Only FOXP3+ lymphocytes in post-NAC breast tissue were a predictive marker for low pCR rate in univariate (OR = 0.41, 95% CI: 0.21-0.80) and multivariate (OR = 0.36, 95% CI: 0.13-0.95) analysis.

Conclusion: Higher TILs levels in pre-treatment biopsy indicated higher pCR rates for NAC. TILs subset played different roles in predicting response to NAC.

Show MeSH
Related in: MedlinePlus