Immune infiltrate in the primary tumor predicts effect of adjuvant radiotherapy in breast cancer; results from the randomized SweBCG91RT trial.

Purpose Tumor-infiltrating immune cells play a key role in tumor progression. The purpose of this study was to analyze if the immune infiltrate predicts benefit from postoperative radiotherapy (RT) in a large randomized breast cancer RT trial. Experimental design In the SweBCG91RT trial, patients with stage I and II breast cancer were randomized to breast conserving surgery (BCS) and postoperative RT or to BCS only and followed for a median time of 15.2 years. The primary tumor immune infiltrate was quantified through two independent methods; immunohistochemistry (IHC) and gene expression profiling. For IHC analyses, the absolute stromal area occupied by CD8+ T cells and FOXP3+ T cells, respectively, was used to define the immune infiltrate. For gene expression analyses, immune cells found to be prognostic in independent datasets were pooled into two groups consisting of antitumoral- and protumoral immune cells, respectively. Results An antitumoral immune response in the primary tumor was associated with a reduced risk of breast cancer recurrence and predicted less benefit from adjuvant RT. The interaction between RT and immune phenotype was significant for any recurrence in both the IHC and gene expression analyses (p=0.039 and p=0.035) and was also significant for IBTR in the gene expression analyses (p=0.025). Conclusions Patients with an antitumoral immune infiltrate in the primary tumor have a reduced risk of any recurrence and may derive less benefit from adjuvant RT. These results may impact decisions regarding postoperative RT in early breast cancer.