Tumor-Infiltrating Lymphocytes and Preoperative Partial Breast Irradiation in Early-Stage Breast Cancer: Insights From the Prospective PAPBI Cohort.

Abstract

Current understanding of the interaction between radiation therapy (RT) and tumor-infiltrating lymphocytes (TILs) is limited. We investigated the impact of preoperative accelerated partial breast irradiation (PAPBI) on TILs in early-stage breast cancer patients. In addition, we evaluated whether baseline TILs were associated with pathologic response to RT. In the prospective PAPBI trial, early-stage breast cancer patients received preoperative RT (10 × 4 or 5 × 6 Gy), followed by a wide local excision after 6 weeks. Matched control patients who underwent postoperative RT were retrospectively collected for validation. Stromal TILs (sTILs) were manually scored on hematoxylin- and eosin-stained slides from diagnostic biopsy and resection specimens, following established guidelines. Baseline differences in sTILs between patients with and without a pathologic complete response (pCR) were analyzed using the Mann-Whitney U test, and longitudinal changes in sTILs were evaluated with a linear mixed model. A total of 72 PAPBI patients and 68 matched controls were included. In the PAPBI cohort, baseline sTILs were generally low, with a median of 2% (IQR, 1%-2%). Eight patients (11%) achieved a pCR, and these patients had significantly higher baseline sTILs compared with patients without a pCR (P = .021). Among the 64 PAPBI patients with evaluable preirradiation and postirradiation samples, a minimal, nonsignificant increase in sTILs was observed following RT. Control patients had similarly low baseline sTILs (median, 2%; IQR, 1%-2%), with no significant changes over time. In this cohort of early-stage breast cancer patients receiving preoperative partial breast irradiation, longitudinal assessment showed minimal changes in sTILs after RT. In patients who achieved a pCR, we observed significantly higher baseline sTILs compared with those without a pCR.