3D architecture results in enhanced BCSC population and modulates HER2 distribution, leading to increased Trastuzumab resistance. Treatment increased the frequency of EMT-like cancer CSCs in HER2+, PTEN− cells through an IL-6 inflammatory feedback loop. miR-2055p is overexpressed in cancer, directly represses HER2, and indirectly represses EGFR through p63 leading to resistance of targeted therapy. The gene discussed is ERBB2; the disease is cancer.