In particular, the IGF pathway seems to be involved in modulating the expression of Epidermal Growth Factor receptors (EGFR) in cancer cells, and, as a consequence, it might have a key role in inducing resistance to endocrine therapies in estrogen receptor (ER)-positive BC patients [12,13]; in addition, direct interactions between the IGF-1R and the HER2 pathway have been reported and may contribute to the resistance to anti-HER2–targeted therapy [14] (Table 1). The gene discussed is ESR1; the disease is cancer.