Clinically, at least 50% of HER2-overexpressing breast cancers are ER+, and this breast cancer subtype is particularly challenging to treat due to its resistance to both anti-estrogen and anti-HER2 therapies (Arpino et al., 2004; Nahta et al., 2006; Chen et al., 2008; Rexer and Arteaga, 2012). The gene discussed is ESR1; the disease is breast cancer.