Abstract: The cytokine TGF?, in the tumor microenvironment, primes cancer cells for metastasis to the lungs. TGF? response status (TBRS) can be determined by comparing expression levels of a panel of genes from cancer cells to the expression levels of the same genes in epithelial cell lines before and after induction with TGF?. A TGF? gene response signature reveals a clinical association between TGF? activity in primary estrogen receptor negative (ER?) tumors and risk of lung metastasis. Further, combining the gene signature of the present invention with the known lung metastasis signature (LMS) increases the predictive value of the LMS considerably.