Association between cardiac radiation dose and coronary artery calcification progression in breast cancer patients after radiotherapy: the modifying role of concomitant systemic inflammation (BACCARAT study)

Radiation-induced cardiotoxicity remains a significant concern in breast cancer (BC) patients treated with radiotherapy (RT), with both cardiac radiation exposure and systemic inflammation emerging as key contributors to early cardiovascular complications. This study investigated whether cardiac radiation dose triggers independently or synergistically with systemic inflammation, characterized by C-reactive protein (CRP) elevation to predict coronary artery calcification (CAC) progression in BC survivors. We analyzed 101 chemotherapy-naïve BC women who underwent cardiac CT before and 24 months after RT, with dosimetric analysis of left ventricle (LV) radiation exposure. Sustained CRP elevation was defined as increased CRP at both end of RT and 6 months post-RT. CAC progression was observed in 28 patients (27.7%). Both sustained CRP elevation (OR = 3.42; 95% CI: 1.12-10.5) and mean LV dose (OR = 1.20 per Gy; 95% CI: 1.03-1.40) were independently associated with CAC progression. Although no statistically significant interaction was observed, stratified analyses showed a stronger association between mean LV dose and CAC progression among patients with sustained inflammation (OR = 1.39, 95%CI: 1.07-1.81), whereas this association was weaker and non-significant in patients without systemic inflammation (OR = 1.12, non-significant). The combined model incorporating both predictors showed improved discriminative performance (AUC = 0.733). These findings suggest that systemic inflammation may amplify the effect of cardiac irradiation and that combining inflammatory and dosimetric data improves early prediction of CAC risk. This may help identify high-risk subgroups who could benefit from enhanced cardiovascular monitoring or preventive strategies after BC RT.