ERBB2 and breast cancer: Thus, in HER2/EGFR-positive breast cancer, GOF mutp53 R175H activates the master heat shock transcription factor Hsf1, which in turn upregulates the heat shock response including HSP90, which then further stabilizes mutp53, HER2 and EGFR.9 This loop likely contributes to the vulnerability of such cancers to Hsp90 inhibition.