More specifically, we show here that the signaling between the tumor cells and the macrophages in the mammary ducts results in (1) increased ductal breakthrough and metastasis with severe splenomegaly, (2) a M1 to M2 macrophage polarization and establishment of an anti-inflammatory microenvironment in support of metastasis, (3) augmented systemic levels of immune-related biomarkers CHI3L1 and LCN2 mirroring disease progression and leukemoid responses. This evidence concerns the gene LCN2 and Splenomegaly.