Sudhan explored the mechanisms through which extended adjuvant neratinib treatment achieved a better clinical outcome in patients with HER2+ER+ breast cancers; these authors have developed a human-in-mouse breast cancer model and, through the analysis of this model, reached the conclusion that HER2+/ER+ tumors rapidly evade ER blockade through ERBB pathway hyperactivation and incomplete suppression of cyclin D1 by estrogen inhibitors, requiring the complete suppression of the effect of nerotinib [108]. The gene discussed is ESR1; the disease is breast cancer.