ERBB2 and breast cancer: Other proposed mechanisms include the constitutive activation of the autophagy-related gene 12 (ATG12) [20], the presence of trastuzumab-refractory breast cancer stem cells (CSCs) [21], and the steric hindrance caused by association of HER2 with other cell surface signaling proteins, i.e. integrins β1, CD44, MUC1 and MUC4 [22].