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

Abstract

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.

Keywords: Breast cancer; mastectomy; radiotherapy; survival; tumor-infiltrating lymphocytes.