For instance, since HER-2 is known to be a member of the epidermal growth factor receptor (EGFR) protein family, and overexpression is seen in ∼20% of breast cancers [64], it can be readily seen by examining the DEABM rule set that there may be a cross-receptor activity between EGFR and HER-2 in breast fibroblasts in response to amphiregulin produced by estrogen-stimulated ER+ luminal cells, which in turn would increase the production of HGF to further stimulate proliferation. The gene discussed is ESR1; the disease is breast carcinoma.