ESR1 and Insulin resistance: The most probable is that it acts as an aromatase substrate for estrogen synthesis [25, 33, 34], but also may favor resistance to hormonal treatment through alternative ER-signaling [37–40], likely by AR-axis, and predisposing to the visceral fat accumulation and to the endocrine-metabolic imbalances associated with insulin resistance, which in turn mediate breast cancer growth [20–22].