Systemic Inflammation After Radiation Predicts Locoregional Recurrence, Progression, and Mortality in Stage II-III Triple-Negative Breast Cancer

Purpose: Patients with triple-negative breast cancer experience high rates of recurrence after radiation, which may be facilitated by the recruitment of circulating tumor cells to proinflammatory microenvironments in the absence of lymphocytes. We hypothesized that patients with lymphopenia and elevated inflammatory hematologic markers after radiation therapy would have an increased risk of locoregional failure.

Methods and materials: With approval, we retrospectively studied a cohort of women treated with adjuvant radiation therapy for stage II-III triple-negative breast cancer. We analyzed the relationship between post-radiation therapy neutrophil:lymphocyte ratio (NLR) and locoregional recurrence by using Cox regression.

Results: One-hundred thirty patients met inclusion criteria, and median follow-up time was 7.6 years. Patients with an NLR ≥3 had a higher rate of locoregional failure (P = .04) and lower overall survival (P = .04). After adjusting for stage (hazard ratio [HR], 5.5; P < .0001) and neoadjuvant chemotherapy (HR, 2.5; P = .0162), NLR was highly predictive of locoregional failure (HR, 1.4; P = .0009). NLR was also highly predictive of overall survival (HR, 1.3; P = .0007) after adjustment for stage and neoadjuvant chemotherapy.

Conclusions: Innate peripheral inflammation after radiation therapy for triple-negative breast cancer in an immunocompromised setting may be a novel prognostic biomarker for locoregional recurrence, progression, and survival. This finding supports preclinical studies of post-radiation therapy inflammation-mediated tumor progression. Further studies are needed to confirm this finding and develop treatment strategies.