The biological significance of leptin-induced upregulation of VEGF and VEGFR2 expression (at protein and mRNA levels) was investigated in breast cancer cells responsive (4T1 and MCF-7; ER+) and unresponsive to estrogen (MDA-MB231; ER−) and derived tumor-xenografts hosting by mice treated with a specific leptin antagonist (pegylated, PEG-LPrA2). This evidence concerns the gene ESR1 and breast carcinoma.