Tumor-infiltrating lymphocytes predict improved overall survival after post-mastectomy radiotherapy: a study of the randomized DBCG82bc cohort

Background The predictive value of tumor-infiltrating lymphocytes (TILs) on the benefit from radiotherapy (RT) remains unclear. Our aim was to investigate the association between TILs and post-mastectomy RT (PMRT) regarding the risk of recurrence and survival in a randomized cohort. Material and methods Stromal TILs were histologically estimated in 1011 tumors from high-risk breast cancer (BC) patients from the DBCG82bc trial. Patients were diagnosed between 1982 and 90, treated with total mastectomy and partial axillary lymph node dissection, randomized to ± PMRT followed by adjuvant systemic treatment. A competing risk model, Kaplan-Meier analysis and multivariate Cox regression analysis were used for correlating TILs and clinical outcome. Results 106 of 1011 patients (10.5%) showed high TILs using a 30% cut-off. In multivariate regression analysis, a high level of TILs was an independent factor associated with lower risk of distant metastasis (DM) and improved overall survival (OS), but without association with loco-regional control. High TILs were associated with a significantly greater OS after PMRT at 20 years compared to low TILs (8% improvement for low TILs (23% to 31%) vs. 22% for high TILs (26% to 48%), interaction-test: p = 0.028). The association between TILs and PMRT was more pronounced among estrogen-receptor negative (ER-) tumors, and patients having ER-/low TILs tumors showed no OS benefit from PMRT at 20 years (-4% improvement for low TILs (28% to 24%) vs. 23% for high TILs (20% to 43%). A similar trend in the association between high TILs and reduced risk of DM after PMRT was seen. Conclusion High TILs predict improved OS from PMRT in BC patients, and the association appeared especially strong for ER- tumors. A trend in the association between high TILs and reduced risk of DM after PMRT was seen. These findings may indicate that RT triggers an immune response inducing a systemic effect outside the treatment field.