The prognostic time dependence of intra-tumoural IFNγ mRNA and protein in patients with breast cancer followed for 14 years after surgery and radiotherapy, without subsequent systemic therapy

There is increasing evidence for the importance of immunity in breast cancer. IFNγ is expected to have a prognostic value based on its major role in innate and specific cell-mediated immunity. In this retrospective study, based on the 14-year follow-up of 73 patients with breast cancer after surgery and radiotherapy but no subsequent systemic therapy, we investigated the prognostic time dependence of intra-tumoural IFNγ mRNA and protein levels. Over the entire 14 years of follow-up, neither IFNγ mRNA nor protein was significantly associated with metastasis outcome by AUC and Cox regression criteria. However, evaluation of the shorter periods has revealed a prognostic significance in the late follow-up period of 7-14 years for IFNγ mRNA and protein with the maximal respective AUCs of 0.72 and 0.73 and hazard ratios of 6.1 and 5.2, respectively. Interestingly, the opposite prognostic association was discovered for IFNγ mRNA and protein in the first 7 years of follow-up, possibly due to the negative correlation of IFNγ protein and mRNA. Moreover, the prognostic association of IFNγ mRNA has shifted from marking the favourable outcome in the first 7 years to poor outcome thereafter. This study contributes to clarification of the previously inconsistent prognostic performance of IFNγ by providing the first prognostic evaluation with long follow-up, time-dependence assessment and absence of any chemotherapy influence.