Tumor-infiltrating lymphocytes to predict survival to anthracycline/taxane-based neoadjuvant chemotherapy in breast cancer.

Abstract

2 Background: Current guidelines have limited information regarding tumour-infiltrating lymphocytes (TILs) were predictive in breast cancer survival treated with neoadjuvant chemotherapy, although some studies suggest a benefit. We quantify the prognostic value of this biomarker for neoadjuvant chemotherapy in patients with breast cancer. Methods: PubMed and EMBASE were searched until March 2017 for studies that investigated the association of TILs with survival for anthracycline/taxane-based neoadjuvant chemotherapy in breast cancer. Overall survival (OS) and disease-free survival (DFS) were combined using random-effects meta-analysis calculated as combined hazard ratio (HR) with 95% credible intervals (CIs). The interaction test was adopted in order to determine the differential effect according to the histology subtypes and TILs subsets. The PROSPERO registry number is CRD42017072133. Results: We identified 16 studies comprising 2,523 patients were entitled. According to histology subtypes analysis indicated that TILs were not prognostic markers for DFS and OS in overall population, but high TILs were related to improved DFS (HR = 0.73, 95% CI, 0.63 – 0.86) and OS (HR = 0.65, 95% CI, 0.51 – 0.83) in triple negative breast cancer (TNBC) patients, and high TILs were also related to better DFS (HR = 0.62, 95% CI, 0.40 – 0.96) in HER2–positive patients. For TILs subsets, our results indicated that high TILs were prognostic markers for DFS (HR = 0.94, 95% CI, 0.89 – 0.98) and OS (HR = 0.74, 95% CI, 0.58 – 0.94). In an ad-hoc analysis, increasing CD8+ lymphocytes were associated with improved DFS (HR = 0.46, 95% CI, 0.33 – 0.65) and OS (HR = 0.41, 95% CI, 0.24 – 0.71), high CD8/FOXP3 ratio was correlated with prolonged DFS (HR = 0.43, 95% CI, 0.29 – 0.63) and OS (HR = 0.45, 95% CI, 0.26 – 0.76), while rich FOXP3+ lymphocytes were associated with reduced DFS (HR = 1.47, 95% CI, 1.01 – 2.15) in overall population. Conclusions: The present results reveal TILs as a predictor of survival to anthracycline/taxane-based neoadjuvant chemotherapy in breast cancer patients. Furthermore, predictive benefit appears to be influenced by breast cancer subtypes and TILs subsets as well.