Iron is a vital element involved in several cellular key processes. Cells acquire iron mostly by the transferrin receptor 1 (TfR1), store it in ferritin (Ft) and may export it by ferroportin (FPN1) under hepcidin (HAMP) regulation. Besides taking up iron for their own survival, circulating leukocytes are also capable of exporting iron in some conditions. We hypothesize that stromal inflammatory cells, by constituting a potential iron delivery system, may have an important role in breast cancer progression. The expression of the most relevant iron metabolism proteins (hepcidin, ferroportin, transferrin receptor 1 and ferritin-H) was assessed by immunohistochemistry in 277 tissue microarray spots from 146 samples, including 116 from mastectomy reductions, 54 from ductal carcinoma in situ (DCIS) and 107 from invasive ductal carcinoma (IDC). Representative lesions of each sample type were evaluated. Human donor liver and liver from Hamp-/- mice were used as staining controls. Breast cancer epithelial cells present an ‘iron-gathering’ phenotype with higher expression of hepcidin, TfR1 and lower Ft-H than in ‘normal’ mastectomy samples, which is compatible with a proliferative status. Conversely, lymphocytes and macrophages display an ‘iron-donor’ phenotype with higher FPN1 and Ft-H expression which fits with the idea of an iron delivery system, while maintaining an activation profile with increased hepcidin and TfR1 expression. Preliminary data suggests that this phenotype may be particularly important during invasive transition as observed by the higher iron export potential in high grade in situ when compared with small-sized invasive lesions. Tumor size is positively correlated with TfR1 expression (R = 0.411, p = 0.005) and hormone receptor negative status with FPN1 (p < 0.05) in epithelial cells.In summary, we demonstrate that lymphocytes and macrophages in breast cancer exhibit a particular ‘iron-donor’ profile that may contribute to the tumor cells nutrition, especially in in situ stages where the iron supply might be critical to the invasive transition.Disclosure: All authors have declared no conflicts of interest. Iron is a vital element involved in several cellular key processes. Cells acquire iron mostly by the transferrin receptor 1 (TfR1), store it in ferritin (Ft) and may export it by ferroportin (FPN1) under hepcidin (HAMP) regulation. Besides taking up iron for their own survival, circulating leukocytes are also capable of exporting iron in some conditions. We hypothesize that stromal inflammatory cells, by constituting a potential iron delivery system, may have an important role in breast cancer progression. The expression of the most relevant iron metabolism proteins (hepcidin, ferroportin, transferrin receptor 1 and ferritin-H) was assessed by immunohistochemistry in 277 tissue microarray spots from 146 samples, including 116 from mastectomy reductions, 54 from ductal carcinoma in situ (DCIS) and 107 from invasive ductal carcinoma (IDC). Representative lesions of each sample type were evaluated. Human donor liver and liver from Hamp-/- mice were used as staining controls. Breast cancer epithelial cells present an ‘iron-gathering’ phenotype with higher expression of hepcidin, TfR1 and lower Ft-H than in ‘normal’ mastectomy samples, which is compatible with a proliferative status. Conversely, lymphocytes and macrophages display an ‘iron-donor’ phenotype with higher FPN1 and Ft-H expression which fits with the idea of an iron delivery system, while maintaining an activation profile with increased hepcidin and TfR1 expression. Preliminary data suggests that this phenotype may be particularly important during invasive transition as observed by the higher iron export potential in high grade in situ when compared with small-sized invasive lesions. Tumor size is positively correlated with TfR1 expression (R = 0.411, p = 0.005) and hormone receptor negative status with FPN1 (p < 0.05) in epithelial cells. In summary, we demonstrate that lymphocytes and macrophages in breast cancer exhibit a particular ‘iron-donor’ profile that may contribute to the tumor cells nutrition, especially in in situ stages where the iron supply might be critical to the invasive transition. Disclosure: All authors have declared no conflicts of interest.