ESR1 and breast cancer: To examine whether PIs can act against ERα+/HER2+ breast cancer cells that express a constitutively active HER2 mutant that confers resistance to trastuzumab and lapatinib and intrinsic resistance to endocrine therapy, MCF7 HER2 insYVMA [40], MCF7 HER2 wt [40] and parental MCF7 cells were cultured in the presence of various carfilzomib or bortezomib concentrations as indicated.