Signs of proinflammatory/genotoxic switch (adipogenotoxicosis) in mammary fat of breast cancer patients: Role of menopausal status, estrogens and hyperglycemia.

The abundance of fat tissue surrounding normal and malignant epithelial mammary cells raises the questions whether such 'adipose milieu' is important in the local proinflammatory/genotoxic shift, which apparently promotes tumor development and worsens prognosis, and what conditions stimulate this shift, or 'adipogenotoxicosis.' We studied 95 mammary fat samples from 70 postmenopausal and 25 premenopausal breast cancer (BC) patients at a distance of 1.5-2.0 cm from tumors. The levels of leptin, adiponectin, TNFα and IL-6 release after 4-hr incubation of the samples were evaluated with ELISA, nitric oxide (NO) production by Griess reaction and lipid peroxidation by determination of thiobarbiturate-reactive products (TBRP). Infiltration of fat with macrophages (CD68-positive cells) and expression of cytochrome P450 1B1/estrogen 4-hydroxylase ( CYP1B1) were detected by immunohistochemistry. Aromatase ( CYP19) activity in mammary fat was measured by [ABSTRACT FROM AUTHOR]