Compelling evidence suggests that breast cancer growth in at least some ER+ and HER2-overexpressing tumours is regulated by bi-directional crosstalk between ER and HER2 signalling pathways that can drive the development of resistance to endocrine therapy (Arpino et al. 2008, Goutsouliak et al. 2020) (Fig. 2). This evidence concerns the gene ESR1 and breast carcinoma.