Given that all HER2 heterogeneous breast cancers subjected to sequencing here were ER-positive, and all but one case was TP53 and/or PIK3CA-mutant, we assessed the effect of forced expression of the HER2 I767M mutation on the growth and HER2 downstream signaling in ER-positive breast cancer cell lines harboring TP53 and/or PIK3CA mutations (that is, MCF7, PIK3CA-mutant; T47D, TP53 and PIK3CA-mutant). The gene discussed is ESR1; the disease is breast cancer.