Abstract

1 Background: Previous clinical data suggested that the tumour-infiltrating lymphocytes (TILs) were predictive in breast cancer treated with adjuvant chemotherapy; however, clinical relevance has yet to be established. We hypothesized that TILs would be associated with overall survival (OS) and disease-free survival (DFS) after anthracycline/taxane-based adjuvant chemotherapy in breast cancer subtypes. Methods: PubMed and EMBASE were searched until March 2017 for studies that investigated the association of TILs with survival for anthracycline/taxane-based adjuvant chemotherapy in breast cancer. OS and DFS were combined using random-effects meta-analysis and calculated as combined hazard ratio (HR) with 95% credible intervals (CIs). The PROSPERO registry number is CRD42017072133. Results: Twelve studies comprising 9,023 patients were eligible for analysis. Six were prospective adjuvant trials (n = 7686) and six were retrospective studies (n = 1337). Pooled analysis indicated that high TILs have no significant predictive association in overall population (DFS, HR = 0.87, 95% CI, 0.70 – 1.08; OS, HR = 0.98, 95% CI, 0.89 – 1.07), Luminal A/B (DFS, HR = 0.99, 95% CI, 0.94 – 1.04; OS, HR = 1.01, 95% CI, 0.92 – 1.12), and HER2–positive patients (DFS, HR = 0.84, 95% CI, 0.71 – 1.00; OS, HR = 0.89, 95% CI, 0.77 – 1.02), but were related to improved DFS (HR, 0.81; 95% CI, 0.73 – 0.89) and OS (HR, 0.74; 95% CI, 0.66 – 0.84) in triple negative breast cancer (TNBC) patients. Additionally, increasing TILs were not significantly associated with reduced risk of relapse in HER2-positive patient through adjuvant trastuzumab (HR, 0.97; 95% CI, 0.93 – 1.01). Conclusions: This meta-analysis provides an evidence that TILs predicts survival to anthracycline/taxane-based adjuvant chemotherapy in TNBC patients and suggests that predictive benefit seemed to be influenced by breast cancer subtypes as well.

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