In addition, the activation status of ERα (e.g., phosphorylation at Ser118, pERα), the Bcl-2 levels, an E2/ERα-dependent apoptosis associated factor [21], and the activation of AKT, one of the ERα-dependent signals important for NGB accumulation in cancer cell lines [16], have been evaluated in G2-grade tumors of pre-and post-menopausal patients. This evidence concerns the gene ESR1 and cancer.