Redução do efluxo de colesterol mediado pela lipoproteína de densidade alta (HDL) e alteração na composição desta lipoproteína em mulheres com câncer de mama

Abstract

The etiopathogenesis of breast cancer is diverse and the molecular classification of tumors and clinical staging are prognostic and predictive tools. Elevated plasma total cholesterol (TC) and reduced high-density lipoprotein cholesterol (HDLc) are considered as possible contributors to the development of breast cancer. Oxygenated cholesterol derivatives - oxysterols (OX) - are increased in hypercholesterolemia and are associated with proliferation and metastasis. Furthermore, they increase cellular oxidative insult and disrupt lipid homeostasis, in part by decreasing the content of the high-density lipoprotein (HDL) receptor, ABCA-1. This impairs cholesterol removal by HDL, increasing intracellular concentration of lipids and OX. In the present study, it was evaluated in newly diagnosed women with invasive breast cancer: a) the concentration of plasma lipids; b) HDL composition in OX, TC, triglycerides (TG), phospholipids (PL), and apoA-I; c) the ability of HDL in removing 14C-cholesterol from macrophages; and d) the association between the aforementioned variables with the molecular classification of the tumor and stage of the disease. Women between 18 and 80 years of age, with a recent diagnosis of breast cancer, treatment-naïve, and in any clinical stage of the tumor were included (n=186). Women without breast cancer were included as a control group (n=150). Plasma lipids were determined by enzymatic assays and apolipoproteins (apo) by immunoturbidimetry. HDL was isolated by plasma discontinuous density gradient ultracentrifugation, and OX determined by gas chromatography coupled with mass spectrometry. HDL-mediated cell cholesterol removal was determined in macrophages previously overloaded with cholesterol and 14C-cholesterol. The frequency of molecular types of breast cancer was: luminal A and B (67.3%), HER2 (16.9%), and triple-negative (TN; 15.8%). Plasma TC, TG, HDLc, cholesterol in low-density lipoprotein (LDLc) and very low-density (VLDLc), CT/apoB, and TG/HDLc were similar between breast cancer and control groups. A higher concentration of TG (27.5%) and VLDLc (31.3%) was observed in TN compared to HER2. Plasma lipids were similar between localized and advanced diseases. A lower concentration of TC (18%), PL (10%), and 27 hydroxicholesterol (38.5%) was observed in the HDL of the breast cancer as compared to the control group. However, cellular cholesterol removal was similar between HDL from both groups. There was no difference in the composition of HDL between the stages of the disease, however, in III and IV stages of disease, cholesterol efflux was 28.6% lower compared to I and II stages. The findings show that the functionality of HDL, impaired in advanced breast cancer, is independent of changes in its composition and plasma lipids.