Prognostic value of systemic inflammation in early-stage breast cancer in the CANTO cohort (SIM-CANTO).

566 Background: The importance of host anti-tumor immunity in early-stage breast cancer (eBC) is now well recognised. Neutrophil / lymphocyte ratio (NLR) is a peripheral blood-based measure of systemic inflammation and immune status that has been associated with prognosis in other tumour types.We aimed to evaluate the prognostic value of NLR in a large prospective cohort of eBC. Methods: Patients with eBC (stage I-III) in the national French CANTO (NCT01993498) cohort with baseline peripheral blood counts (obtained after diagnosis and before any eBC treatment, including surgery) were included, regardless of systemic (neo)adjuvant therapy. The independent variable of interest was baseline NLR assessed as a continuous variable. Outcomes included invasive- and distant-disease-free survival (iDFS, DDFS) and overall survival (OS). We performed univariable analysis followed by multivariable Cox regression models sequentially adjusting for age, biologic subtype, TNM stage and treatment. Main analyses were conducted in the overall cohort, while additional analyses explored the role of NLR in subtypes (ER+/HER2-, HER2+, TNBC). For a cohort of patients receiving neoadjuvant therapy we tested the impact of NLR or pCR using Wilcoxon test. Sensitivity analyses used NLR as a categorical variable (using median NLR as cutoff to define high vs low NLR). Results: Overall, 10 470 patients were included. Median follow-up was 6.7 years (5.1 – 8.5). The median age at diagnosis was 56.4 years. Most (78%) of patients had stage I/II eBC, 77% ER+/HER2-, 13% HER2+ and 9% TNBC. The median NLR was 2.03. In the univariate analysis, there was a significant association between increasing NLR and worse DDFS in the overall cohort (HR: 1.1, p = 0.004; 95% CI:1.1 – 1.16) and in the ER+/HER2- cohort (HR: 1.1; p = 0.03; 95%CI:1.1 – 1.2 ). In a model adjusted by age and biologic subtype, NLR showed significant associations with DDFS (HR 1.07; p = 0.04) in the global cohort, but these associations did not maintain significance after further adjustment for TNM stage and treatment. Similarly, in the ER+/HER2- cohort, NLR was significantly associated with DDFS when adjusted for age (HR 1.08; p = 0.02), which was no longer significant after adjusting for TNM stage. No statistically significant differences were observed across other subtypes for DDFS, iDFS or OS, nor for pCR in the neoadjuvant cohort. Sensitivity analysis showed consistent results, in particular low NLR was significantly associated with improved DDFS (HR: 0.8, p = 0.03; 95%CI: 0.7 – 0.9) in the ER+/HER2- subgroup. Conclusions: Systemic inflammation, as measured by baseline NLR, was associated with significantly shorter DDFS in the overall CANTO cohort and in the ER+/HER2- subgroup in univariable and age- adjusted analysis. However, this association disappeared after adjustment for known clinicopathologic prognostic characteristics.