HER2 Mutation/Alteration: HER2 is overexpressed in 25–30% of human breast tumors, which has a predictive role for prognosis in the process of chemotherapy and endocrine therapy.4, 12, 70 The HER2 pathway engages in crosstalk with ER and growth factor receptor pathways and as such has a role in endocrine therapy resistance in breast cancer. This evidence concerns the gene ESR1 and breast cancer.