Hypoxic primary breast tumors secrete lysyl oxidase-like 2 (LOXL2), a copper-dependent amine oxidase64 that crosslinks collagen with elastin to generate a stiffened extracellular matrix (ECM), to generate “pre-metastatic niches” that support metastatic colonization and outgrowth61,65,66. Here, LOXL2 is linked to breast neoplasm.