Given that the G2M checkpoint occurs between the G2 and M phases whereas E2F plays a major role during the G1/S transition, we hypothesized that tumors with increased E2F transcriptional activity, measured by scoring the gene expression of E2F target genes, will have characteristics of more aggressive disease as well as a better response to systemic chemotherapy among patients with ER-positive/HER2-negative breast cancer. Here, ESR1 is linked to breast cancer.