Iron-binding proteins and C-reactive protein in Nipple Aspirate Fluids: role of Iron-driven inflammation in breast cancer microenvironment?

Breast cancer, a worldwide disease with increasing incidence, develops from ductal/lobular epithelium. Nipple aspirate fluid (NAF), secreted from the breast ducts and lobules, can be analyzed to assess metabolic activity in breast microenvironment. Premalignant and malignant cell alterations may produce biochemical signals that deliver inflammatory proteins to the site. C-reactive protein (CRP), acute-phase protein considered a prognostic marker of inflammation, is frequently over-expressed in invasive breast carcinomas. Starting from the evidence that soluble and cell-bound iron binding protein Ferritin (FTN) and Transferrin (TRF) are crucially involved in breast inflammation and cancer, the aim of the present study is to analyze in NAF (a ductal fluid mirroring the breast microenvironment noninvasively collected from healthy and proven breast cancer affected women, n=38), the concentrations of CRP, FTN and TRF through high sensitive immunoassays. We analysed also serum (n=35) and milk samples (n=20) from healthy subjects. The mean level of CRP in Cancer NAF was significantly higher than in NoCancer NAF (P < 0.0001), especially in postmenopausal patients. Moreover, in Cancer NAF we detected higher levels of TRF and FTN respect to NoCancer NAF (P<0.001). A highly significant positive correlation between FTN and CRP content (Y= 2322x + 6.196, r(2) = 0.651, P<0.0001) was found. These data may support the involvement of inflammation and deregulation of iron homeostasis in breast cancer etio-pathogenesis. The significant accumulation of CRP in NAF in conjunction to the disruption of iron homeostasis may help to identify women at higher breast cancer risk.