Obesity is associated with chronic low-grade inflammation and elevated levels of circulating inflammatory biomarkers, i.e., C-reactive protein (CRP). Obesity is associated with impaired prognosis in breast cancer (BC), potentially augmented by inflammation. We hypothesize that high levels of CRP are associated with BC outcomes and that the association is more pronounced in patients with obesity.
Female patients (stage I-III) seen at Aarhus University Hospital under diagnostic work-up for BC were asked to donate blood for research (Mar. 2010 – Aug. 2020). CRP levels were measured in serum samples and divided into quartiles with the lowest quartile, Q1, as the reference. We used Cox proportional hazards regression to estimate crude and adjusted hazard ratios (HRs) with 95% confidence intervals (95% CI) to compare BC outcomes in CRP quartiles. Multivariate analyses were adjusted for age, menopausal status, tumor grade, stage, surgery type, systemic adjuvant treatment, radiotherapy, comorbidities, and body mass index, and stratified by estrogen receptor status.
Among the 4,190 patients who donated blood, 2,676 patients were included following exclusion of 1,514 patients with e.g. benign disease or previous cancer history. During 15,249 person-years of follow-up, 225 recurrences occurred (69 locoregional and 156 distant metastases). Patients with high CRP (Q4) had a higher risk of BC event compared with patients with low CRP (Q1) (HRadj: 1.59 (95% CI 1.13-2.24)). Among patients with normal-weight and obesity, the HRadj was 1.57 (95% CI 0.95-2.59) and 0.89 (95% CI 0.21-3.86), respectively. In overall survival analyses, Q4 was associated with inferior prognosis compared to Q1 (HRadj: 2.40 (95% CI 1.60-3.61)). In patients with normal-weight the association was evident (HRadj: 3.46 (95% CI 1.94-6.18)) whereas, in patients with obesity, CRP was not associated with OS (HRadj: 0.69 (95% CI 0.15-3.07)).
CRP levels at diagnosis seem prognostic in early BC. In patients with normal-weight, high CRP was associated with inferior disease-free and overall survival, however, in patients with obesity, CRP was not prognostic. Thus, CRP levels may help to distinguish patients with a better or worse BC prognosis among patients with normal-weight, but not obesity.
The authors.
Novo Nordisk Foundation, NEYE Foundation, The Danish Cancer Society, Fagerlund Stifelsen and the Department of Oncology Research Foundation.
All authors have declared no conflicts of interest.