Impact of radiotherapy-induced inflammatory responses on progression-free survival in a tri-racial/ethnic breast cancer population

Background Inflammatory biomarker C-reactive protein (CRP) is associated with breast cancer risk and survival. We examined whether CRP levels before radiotherapy (pre-RT), after RT (post-RT), and RT-induced change impact breast cancer progression-free survival (PFS). Methods Plasma high-sensitivity CRP was measured, and patients were followed for up to 13 years after RT. PFS was calculated from the date of diagnosis to the date of disease progression or the last date of follow-up. Univariable and multivariable Cox proportional hazards regression models were used to evaluate the associations between CRP and PFS adjusted for other patient/clinical variables. Results In 469 patients (64 non-Hispanic Whites, 303 Hispanic Whites, and 102 African Americans), post-RT CRP levels were significantly higher in patients with progression compared to progression-free patients (mean±SD: 12.2±15.4 mg/L vs. 7.3±11.5, p=0.011). In univariable analyses, worse PFS was significantly associated with post-RT CRP ≥5.1 mg/L (hazard ratio [HR]: 2.67; 95% confidence interval [95% CI]: 1.65-4.30) and CRP change ≥2.3 mg/L (HR: 3.55; 95% CI: 2.25-5.64). In multivariable models, post-RT CRP ≥5.1 mg/L was associated with worse PFS in all (HR: 2.10; 95% CI: 1.29-3.42) or patients with tumor stage III (HR: 2.93, 95% CI: 1.20-7.18). CRP change ≥2.3 mg/L was associated with worse PFS in all (HR: 2.38; 95% CI: 1.45-3.92) or patients with tumor stage III (HR: 2.41, 95% CI: 1.09-5.33). Conclusions Our data suggest that an RT-induced hyper-inflammatory response may contribute to worse breast cancer PFS. Future larger studies are warranted to validate our findings and guide follow-up surveillance and targeted interventions.