Abstract
The prognostic value of current multigene assays for breast cancer is limited to hormone receptor-positive, human epidermal growth factor receptor 2-negative early breast cancer. Despite the prognostic significance of immune response-related genes in breast cancer, immune gene signatures have not been incorporated into most multigene assays. Here, using public gene expression microarray datasets, we classified breast cancer patients into three risk groups according to clinical risk and proliferation risk. We then developed the immune prognostic index based on expression of five immune response-related genes (TRAT1, IL2RB, CTLA4, IGHM and IL21R) and lymph node status to predict the risk of recurrence in the clinical and proliferation high-risk (CPH) group. The 10-year probability of disease-free survival (DFS) or distant metastasis-free survival (DMFS) of patients classified as high risk according to the immune prognostic index was significantly lower than those of patients classified as intermediate or low risk. Multivariate analysis revealed that the index is an independent prognostic factor for DFS or DMFS. Moreover, the C-index revealed that it is superior to clinicopathological variables for predicting prognosis. Its prognostic significance was also validated in independent datasets. The immune prognostic index identified low-risk patients among patients classified as CPH, regardless of the molecular subtype of breast cancer, and may overcome the limitations of current multigene assays.
Highlights
The prognostic value of current multigene assays for breast cancer is limited to hormone receptorpositive, human epidermal growth factor receptor 2-negative early breast cancer
Among the 1327 patients in the five Gene Expression Omnibus (GEO) datasets, 916 with early breast cancer who were not treated with chemotherapy were included in the discovery dataset
We identified the most significant immune response-related genes associated with clinical outcome in a pre-specified clinical and proliferation high-risk (CPH) subgroup and developed a novel immune prognostic index for this subgroup based on a combination of five immune response-related genes and LN status
Summary
The prognostic value of current multigene assays for breast cancer is limited to hormone receptorpositive, human epidermal growth factor receptor 2-negative early breast cancer. Several multigene assays, including Oncotype DX1, MammaPrint[2], PAM50 Prosigna[3], and E ndoPredict[4] were developed to predict the risk of recurrence or response to adjuvant chemotherapy in those with early breast cancer These assays provide additional prognostic value and support traditional clinical factors. Based on a previous study in which we showed a significant association between immune response-related genes and favorable outcomes in patients with highly proliferating tumors, regardless of ER status, we aimed to develop the immune gene-based prognostic model to further predict the risk of recurrence of high-risk early breast cancer, regardless of molecular subtype. We developed a novel prognostic model based on combined expression of five immune response-related genes and LN status and used it to predict the risk of recurrence in high-risk patients with early breast cancer
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
