A gene signature to predict high tumour-infiltrating lymphocytes after neoadjuvant chemotherapy and outcome in patients with triple negative breast cancer

Abstract

Introduction: In patients with triple-negative breast cancer (TNBC), the extent of tumor-infiltrating lymphocytes (TILs) in the residual disease (RD) after neoadjuvant chemotherapy (NACT) is associated with better prognosis. Our objective was to develop a gene signature from pre-treatment samples to predict the extent of TILs after NACT, and then to test its prognostic value on survival.Patients and Methods: Using 99 pre-treatment samples, we generated a four-gene signature associated with high post-NACT TILs. Prognostic value of the signature on distant relapse-free survival (DRFS) was first assessed on the training set (n = 99) and then on an independent validation set (n = 115).Results: A four-gene signature combining the expression levels of HLF, CXCL13, SULT1E1, and GBP1 was developed in baseline samples to predict the extent of lymphocytic infiltration after NACT. In a multivariate analysis performed on the training set, this signature was associated with DRFS (HR: 0.28 for a one-unit increase in the value of the four-gene signature, 95%CI: 0.13-0.63). In a multivariate analysis performed on an independent validation set, the four-gene signature was significantly associated with DRFS (HR: 0.17, 95%CI: 0.06-0.43). The four-gene signature added significant prognostic information when compared to the clinicopathologic pre-treatment model (likelihood ratio test in the training set p = 0.004 and in the validation set p = 0.002).Conclusion: A four-gene signature predicts high levels of TILs after anthracycline-containing NACT and outcome in patients with TNBC and adds prognostic information to a clinicopathological model at diagnosis.