Circulating C-reactive protein levels as a prognostic biomarker in breast cancer across body mass index groups

Abstract

Purpose Obesity and systemic inflammation are associated with breast cancer (BC) outcomes. Systemic inflammation is increased in obesity. We examined the association between C-reactive protein (CRP) and disease-free survival (DFS) and overall survival (OS) overall, and according to body mass index (BMI). Methods We assembled a cohort of women with BC (stage I-III) seen at Aarhus University Hospital between 2010 and 2020 who donated blood at BC diagnosis (N = 2,673). CRP levels were measured and divided into quartiles. We followed patients from surgery to recurrence, contralateral BC, other malignancy, death, emigration, or end-of-follow-up. We used Cox regression to estimate hazard ratios (HRs) with 95% confidence intervals (95%CIs) to compare outcomes across CRP quartiles, overall and stratified by BMI (normal-weight (18.5 ≤ BMI < 25 kg/m²), overweight (25 ≤ BMI < 30 kg/m²), and obesity (BMI ≥ 30 kg/m²)). Results During follow-up, 368 events (212 recurrences, 38 contralateral BCs, and 118 deaths) occurred (median follow-up 5.55 years). For DFS, high CRP (CRP ≥ 3.24 mg/L) was associated with an increased risk of events (HR_adj:1.58 [95%CI = 1.12–2.24]). In BMI-stratified analyses, high CRP was associated with elevated risk of events in normal-weight and overweight (HR_adj:1.70 [95%CI = 1.09–2.66]; HR_adj:1.75 [95%CI = 1.08–2.86]), but in obesity, the estimate was less precise (HR_adj:1.73 [95%CI = 0.78–3.83]). For OS, high CRP was associated with increased risk of death (HR_adj:2.47 [95%CI = 1.62–3.76]). The association was strong in normal-weight and overweight (HR_adj:3.66 [95%CI = 1.95–6.87]; HR_adj:1.92 [95%CI = 1.06–3.46]), but less clear in obesity (HR_adj:1.40 [95%CI = 0.64–3.09]). Conclusion High CRP levels at BC diagnosis were associated with inferior prognosis in early BC irrespective of BMI, although less clear in patients with obesity.