[en] Background: The immune system has a role in breast tumor, in particular in triple negative (TNBC) and in hormone receptor-negative/HER2-positive breast cancers. The aim of this study is to analyze the association between baseline cytokines expression with cancer relapse and outcome.
Material and methods: Baseline plasmatic samples of 66 stage I-III breast cancers treated with surgery with or without radiotherapy and systemic treatment between 2011 and 2017 were collected. A panel of 24 cytokines were analyzed by Luminex MAGPIX technology, using multiplex
Luminex Magnetic Assay kits (®R&D System).
Results: Sixty-six breast cancer patients were included in the study. The median follow-up was of 78 months (range 18-99). The median age at diagnosis was of 58.5 years (range 32-86). The stage at diagnosis was I in 29 (43.9%) patients, II in 26 (39.4%) and III in 11 (16.7%). The histological type was ductal in 47 cases (71.2%), lobular in 13 (19.7%) and mixed in 6 (9.1%). Fifty-three (80.3%) patients were estrogen-receptor-positive, 11 (16.7%) HER2-positive and 12 (18.2%) TNBC. All the patients received surgery, combined with neo/adjuvant chemotherapy in 35 (53%) cases, anti-HER2 in 9 (13.6%), hormonotherapy in 53 (80.3%) and radiotherapy in 52 (78.8%). During the follow-up we observed 11 relapses and 4 deaths. IL-4 was associated with relapse, that occurs in 30.7% of the cases in the group with IL-4 > 0.07 (IL4-H) mean fluorescence intensity (MFI) vs in 7.5% in the group with IL-4 ⩽ 0.07 MFI (IL4-L) (p 0.013), with a ROC curve AUC of 0.745. In multivariate analysis relapse was associated with IL-13 (p 0.048) and T stage (p 0.049). Survival analysis showed a better time to treatment failure (TTF) for the group IL4-L (5y-TTF 87% vs 63% for IL4-L and IL4-H, p 0.022) and for the group with IL-13 ⩽ 0.1 MFI (IL13-L) compared IL-13 > 0.1 MFI (IL13-H) (5y-TTF 90% vs 45%, p 0.017). A separation of the curves was also observed for breast cancer specific survival (5y-BCSS: 95% vs 84% for IL4-L vs IL4-H, p 0.118; 91% vs 75% for IL13-L vs IL13-H, p 0.029).
Conclusions: Higher baseline plasmatic level of IL-4 and IL-13 are associated with a worse prognosis in early stage breast cancer. These are two structurally and functionally related cytokines known for regulating the immune system activity, leading to a T helper-2 response and to a macrophage M2 polarization. Data should be confirmed in a larger cohort and a mechanistic study is advisable.
