NF1 loss-of-function mutations, RTKs mutations such as ERBB2 activating mutations, as well as alterations in other MAPK pathway genes (EGFR, KRAS, BRAF, and MAP2K1) were found to be enriched in endocrine-resistant advanced ER+ breast cancer compared to early-stage ER+ breast cancer. The gene discussed is MAP2K1; the disease is breast cancer.