In HR-positive/HER2-low BC, bidirectional crosstalk between the estrogen receptor (ER) and the HER2/HER3 axis can drive ET resistance, whereby upregulation of heuregulin and HER2/HER3 heterodimers can phosphorylate the ER, and ER signaling can upregulate HER2 and HER3 expression [18,39]. Here, ESR1 is linked to breast cancer.