Thus, the association of high SRF-independent/SAP-dependent gene expression with reduced DMFS among patients not receiving adjuvant therapy, as well as among LN-negative, ER-positive, Grade 1 and 2 patients indicates that increased expression of the SAP-dependent Mkl1 target genes plays a significant role in the natural metastatic progression of non-aggressive towards highly aggressive breast cancer in human patients. Here, ESR1 is linked to breast cancer.