A gene signature of chemo-immunization to predict outcome in patients with triple negative breast cancer treated with anthracycline-based neoadjuvant chemotherapy

Abstract

Background: The extent of tumor-infiltrating lymphocytes (TILs) in the residual disease after anthracycline-based neoadjuvant chemotherapy (NACT) is associated with a better prognosis, in patients with triple-negative breast cancer (TNBC).We aimed to develop a genomic signature from pre-treatment samples to predict the extent of TILs after NACT, and then to test its prognostic value on survival. Methods: Using 99 pre-treatment samples (training set), we generated a four-gene signature that predicts post-NACT TILs using the LASSO technique. Prognostic value of the signature on survival was first assessed on the training set (n=99) and then evaluated on an independent validation set including 185 patients with TNBC treated with NACT. Results: A four-gene signature combining the expression levels of HLF, CXCL13, SULT1E1, and GBP1 predicted the extent of lymphocytic infiltration after NACT. In a multivariate analysis performed on the training set, a one-unit increase in the signature value was associated with distant-relapse free survival (DRFS) (HR: 0.28, 95%CI: 0.13- 0.63, p=0.0018). For the validation dataset, the four-gene signature was significantly associated with DRFS in the entire set (HR: 0.26, 95%CI: 0.11-0.59, p=0.0012) and in the subset of patients with residual disease (HR: 0.23, 95%CI: 0.10-0.55, p=0.0008). Conclusions: We developed a four-gene signature of immune-activation, which predicts outcome in patients treated with NACT for TNBC.