Prognostic role of preoperative circulating systemic inflammatory response markers in primary breast cancer: meta-analysis

BACKGROUND: Circulating markers of the systemic inflammatory response are prognostic in several cancers, but their role in operable breast cancer is unclear. A systematic review and meta-analysis of the literature was carried out. METHODS: A search of electronic databases up to August 2020 identified studies that examined the prognostic value of preoperative circulating markers of the systemic inflammatory response in primary operable breast cancer. A meta-analysis was carried out for each marker with more than three studies, reporting a HR and 95 per cent confidence interval for disease-free survival (DFS), breast cancer-specific survival (BCSS) or overall survival (OS). RESULTS: In total, 57 studies were reviewed and 42 were suitable for meta-analysis. Higher neutrophil-to-lymphocyte ratio (NLR) was associated with worse overall survival (OS) (pooled HR 1.75, 95 per cent c.i. 1.52 to 2.00; P < 0.001), disease-free survival (DFS) (HR 1.67, 1.50 to 1.87; P < 0.001), and breast cancer-specific survival (BCSS) (HR 1.89, 1.35 to 2.63; P < 0.001). This effect was also seen with an arithmetically-derived NLR (dNLR). Higher platelet-to-lymphocyte ratio (PLR) was associated with worse OS (HR 1.29, 1.10 to 1.50; P = 0.001) and DFS (HR 1.58, 1.33 to 1.88; P < 0.001). Higher lymphocyte-to-monocyte ratio (LMR) was associated with improved DFS (HR 0.65, 0.51 to 0.82; P < 0.001), and higher C-reactive protein (CRP) level was associated with worse BCSS (HR 1.22, 1.07 to 1.39; P = 0.002) and OS (HR 1.24, 1.14 to 1.35; P = 0.002). CONCLUSION: Current evidence suggests a role for preoperative NLR, dNLR, LMR, PLR, and CRP as prognostic markers in primary operable breast cancer. Further work should define their role in clinical practice, particularly reproducible thresholds and molecular subtypes for which these may be of most value.