Predictive value of improvement in the immune tumour microenvironment in patients with breast cancer treated with neoadjuvant chemotherapy

BACKGROUND: Tumour-infiltrating lymphocytes (TILs) can be used to monitor the immune tumour microenvironment (iTME) and predict treatment response and outcome in breast cancer. We evaluated the prognostic significance of the levels of CD8(+) TILs and forkhead box protein (FOXP3)-positive TILs before and after neoadjuvant chemotherapy (NAC). PATIENTS AND METHODS: We examined 136 patients with breast cancer treated with NAC. The number of CD8(+) TILs and FOXP3(+) TILs in biopsy specimens and residual tumours was evaluated by immunohistochemistry. RESULTS: Patients with a high rate of change in the CD8/FOXP3 ratio (CFR) had significantly better recurrence-free survival (RFS) (p<0.001, log-rank). In multivariate analysis, the rates of change in the CD8(+) TIL levels and the CFR were independent predictors for RFS (HR=2.304, p=0.036 and HR=4.663, p<0.001). In patients with triple-negative and hormone receptor-positive breast cancer, the rate of change in the CFR was an independent predictor for RFS (HR=13.021, p=0.002 and HR=4.377, p=0.003). CONCLUSION: Improvement in the iTME following NAC is correlated with good outcome. The rate of change in the CFR may be a useful biomarker to predict prognosis of patients treated with NAC.