Impaired HDL-mediated cell cholesterol removal in advanced breast cancer

Background and Aims: HDL cholesterol (HDLc) and breast cancer (BC) association is partially controversial because its plasma levels do not reflect HDL particle’s functionality. HDL removes cell cholesterol and oxysterols limiting tumor growth and metastasis. Methods: It was addressed in newly diagnosed, treatment-naïve BC women (n=163) as compared to control women (n=150) the HDL ability in removing cell cholesterol and its composition in lipids, apolipoprotein A-I and oxysterols. HDL was isolated by ultracentrifugation; lipids (total cholesterol, TC; triglycerides, TG; and phospholipids, PL) were determined by enzymatic assays, apo A-I by immunoturbidimetry, and oxysterols (27, 25, and 24-hydroxycholesterol), by gas chromatography coupled with mass spectrometry. HDL-mediated cholesterol removal was determined in macrophages previously overloaded with cholesterol and 14C-cholesterol. Comparisons were done by Mann-Whitney and Kruskal-Wallis tests. Results: Lipid profile was similar between control and BC groups after adjustment per age. In BC, HDL composition in TC, TG, PL, and 27-hydroxicholesterol was reduced (respectively 84%, 93%, 89%, and 61%; P<0.05) as compared to controls, but cell cholesterol removal was similar. Reduced cholesterol efflux (28%; P=0.01) was observed in HDL from advanced BC cases (stages III and IV), as compared to stages I and II, independently of BC histological type. Conclusions: The impaired ability of HDL in removing cell cholesterol and its reduced content in lipids and oxysterol is independent of HDLc plasma levels and may contribute to worsening BC prognosis.