Avaliação de quimiocinas circulantes em pacientes com câncer de mama, o ardiloso luminal b e as misteriosas quimiocinas

Abstract

Introduction: Breast cancer is a heterogeneous disease. The main prognostic factors are staging and tumor subtypes according to immunohistochemistry. These prognostic groupings allow a more standardized treatment, but still not ideal. There is great variability in the therapeutic response, as in Luminal B tumors, which express hormone receptors but show an erratic response to hormone therapy and chemotherapy. The aim of this study is to improve prognostic stratification, in addition to staging and immunohistochemistry, of patients with breast cancer. Methodology: A prospective study with 234 women with infiltrating ductal carcinoma, grouped by TNM staging and immunohistochemistry into Luminal A and B, HER2, and TN subtypes, to analyze survival according to these groups, and their correlation with the value of the Neutrophil/Lymphocytes by hemogram. An equitable selection of 1/3 of these patients, between stages and subtypes by immunohistochemistry, was analyzed for correlations of serum chemokine expressions. We analyzed 7 CC chemokines [CCL2 (MCP1), CCL3 (MIP1α), CCL4 (MIP1β), CCL5 (Rantes), CCL11 (Eotaxin), CCL17 (TARC), CCL20 (MIP3α)], 6 CXC chemokines [CXCL1 (GroAlpha), CXCL5 (ENA78), CCXCL8 (IL-8), CXCL9 (MIG), CXCL10 (IP10), CXCL11 (ITAC)], and 3 cytokines (IL-6, TNF-α, IL-10). In these selected patients, the correlations of the inflammatory infiltrate in the tumor microenvironment were also analyzed according to the expression of T CD8, T CD4, T CD4/FOXP3 lymphocytes, and EGFR. Results: Overall survival was significantly dependent on tumor staging and subtypes by immunohistochemistry, with better survival for women with Luminal A and HER2+ tumors, and worse for Luminal B and TN. There were age correlations with the cytokines IL-6 (r = +0.2392; p = 0.0416) and IL-10 (r = +0.3027; p = 0.0092) and with the chemokine IP10/CXCL10 (r = +0.4360; p = 0.0079). An inverse correlation was found between BMI and the chemokine Rantes/CCL5 (r = -0.3098; p = 0.0169), and weight with Eotaxin/CCL11 (r = -0.2575; p = 0.0470). Kaplan-Meier curves showed that patients with Luminal B breast cancer had a higher risk of death with a Neutrophil/Lymphocyte ratio value >2 (Log-Rank p = 0.005). By analyzing the serum, patients of the Luminal B subtype who expressed lower concentrations of ENA78/CXCL5 (≤ 254.83 pg/ml) (Log-Rank p = 0.016) and of MIG/CXCL9 (≤ 109.28 pg/ml) (Log-Rank p = 0.046), and higher expression of MIP1β/CCL4 (> 34.84 pg/ml) (Log-Rank p = 0.014) showed a higher risk of death. In the analysis of the tumor microenvironment, Luminal B with infiltration of CD4 T Lymphocytes > 30% (Log-Rank p = 0.027) and CD4 + T CD8 Lymphocytes > 75% (Log-Rank p = 0.033) also had a higher risk of death. Conclusion: Patients with Luminal B breast tumors can be better stratified by the expression of Neutrophils and Lymphocytes in the blood count, by the analysis of the expression of serum chemokines, or by the infiltration of T Lymphocytes in the tumor microenvironment, opening new target-specific therapeutic approaches, associated or not with traditional chemotherapy and endocrinotherapy.