The Role of C-Reactive Protein as a Prognostic Biomarker in Patients with Early Breast Cancer Treated with Neoadjuvant Chemotherapy.

ABSTRACT

Background: C-reactive protein (CRP) is an acute phase reactant influenced by inflammation and tissue damage. Elevated CRP levels have been associated with poor outcome of various cancers including breast cancer. However, evidence regarding a potential impact of CRP levels on outcome of neoadjuvant chemotherapy (NACT) in patients with early breast cancer (EBC) is insufficient. Methods: Patients who had received NACT for EBC and had available data regarding CRP levels before therapy, pathologic complete remission (pCR), and follow-up were included. The association between CRP at baseline and outcome parameters was analyzed. Results: 152 women were included in this analysis; median follow-up was 5.8 years. No association between CRP at baseline and pCR rates could be detected. 6.6% of the patients developed a local recurrence, 10.5% developed a distant recurrence, and 5.2% died from breast cancer. A negative correlation (Spearman-Rho) between CRP at baseline and overall survival (OS) (correlation coefficient (CC) -0.255; p = 0.45), disease-free survival (DFS) (CC -0.348; p = 0.075), local recurrence-free survival (LRFS) (CC -0.245; p = 0.327), and distant DFS (DDFS) (CC -0.422; p = 0.057) was not statistically significant, although especially in DFS and DDFS a strong trend was detected. The probability of death from breast cancer was 2% if the CRP was <0.08 mg/dL and 40% if the CRP was >2.08 mg/dL; this association was highly statistically significant (χ2; p < 0.001). These results were independent from age, estrogen and progesterone receptor status, HER2 status, nodal status, and grading. The hazard ratio for OS was 5.75 (p = 0.004) for CRP <0.08 mg/dL versus CRP >2.08 mg/dL. Discussion/Conclusion: CRP at baseline is not predictive for pCR in EBC after NACT in our patient dataset. However, an association of parameters of long-term prognosis with CRP could be demonstrated. Although the correlations of higher CRP levels at baseline and shorter OS, DFS, LRFS, and DDFS were not significant, a strong trend could be detected that was reproduced in the analysis of different groups of CRP levels and the probability of breast cancer mortality. Higher CRP levels are indicating a worse prognosis in EBC after NACT in this retrospective analysis. These results justify further investigation of CRP not as a predictive parameter for pCR but as a biomarker of long-term prognosis in EBC in prospective trials and may lead to therapeutic approaches with the aim of lowering CRP levels.