In this study, we have clearly shown that primary metastatic breast tumors were able to modulate the expression levels of ECM structural proteins (Col14A1, Col4A5, Col5A1, Col15A1), ECM degrading enzymes (MMP2, MMP3, MMP9, MMP13, and MMP14), and ECM processing proteins (LOX, LOXL2, P4HA1) in premetastatic lungs prior to the arrival of the first cancer cells. This evidence concerns the gene COL4A5 and cancer.