Longitudinal changes in NT-proBNP after breast cancer radiotherapy: clinical determinants of its trajectory and association with cardiac dysfunction (BACCARAT study)

Radiotherapy (RT) for breast cancer (BC) may induce subclinical myocardial injury. Longitudinal trajectories of N-terminal pro-B-type natriuretic peptide (NT-proBNP), a biomarker of myocardial stress, remain insufficiently characterized. We aimed to assess changes in NT-proBNP over 2 years after RT, identify clinical and treatment-associated factors, and evaluate associations with cancer therapy-related cardiac dysfunction (CTRCD).

NT-proBNP was measured before RT, at RT completion, and at 6 and 24 months among 101 BC patients treated with adjuvant RT without chemotherapy. Echocardiography was performed longitudinally, and CTRCD was defined according to 2022 ESC Cardio-Oncology guidelines. Factors associated with NT-proBNP trajectories were analyzed using linear mixed-effects models. Logistic regression assessed associations between NT-proBNP and CTRCD.

NT-proBNP remained stable at the end of RT and at 6 months but increased at 24 months (β = 0.147, p < 0.0001; +16%). Baseline NT-proBNP was strongly associated with follow-up levels. Hypercholesterolemia (β = 0.252, p = 0.01), slightly moderate hypofractionated RT (20 × 2.35 Gy; β = 0.372, p = 0.0008), and aromatase inhibitor therapy (β = 0.258, p = 0.019) were independently associated with higher NT-proBNP at 24 months, whereas cardiac dose metrics were not. Seventeen patients developed CTRCD. NT-proBNP > 400 ng/L at 24 months was associated with CTRCD (OR = 6.5, 95% CI 1.24-33.85; p = 0.027).

NT-proBNP increased 2 years after breast RT and was associated with baseline level, cardiometabolic, RT fractionation, and endocrine factors. Elevated NT-proBNP could help to identify BC patients at higher risk of subclinical cardiac dysfunction, supporting longitudinal biomarker monitoring in cardio-oncology surveillance.