Radiosensitivity is associated with antitumor immunity in estrogen receptor-negative breast cancer

Abstract Purpose: This study evaluated radiosensitivity and the tumor microenvironment (TME) to identify characteristics of breast cancer patients who would benefit most from radiation therapy.Methods: We analyzed 1,903 records from the Molecular Taxonomy of Breast Cancer International Consortium cohort using the radiosensitivity index (RSI) and gene expression deconvolution algorithms, CIBERSORT and xCell, that estimates the TME composition of tumor samples. In this study, patients were stratified according to TME and radiosensitivity. We performed integrative analyses of clinical and immuno-genomic data to characterize molecular features associated with radiosensitivity.Results: Radiosensitivity was significantly associated with activation of antitumor immunity. In contrast, radioresistance was associated with a reactive stromal microenvironment. The immuno-genomic analysis revealed that estrogen receptor (ER) pathway activity was correlated with suppression of antitumor immunity. In ER-negative disease, the best prognosis was shown in the immune-infiltrated and radiosensitive group patients, and the lowest was in the immune-excluded and radioresistant group patients. In ER-positive disease, immune signature and radiosensitivity had no prognostic significance.Conclusions: Taken together, these results suggest that tumor radiosensitivity is associated with activation of antitumor immunity and a better prognosis, particularly in patients with ER-negative breast cancer.