ERBB2 and breast cancer: In ESR1-positive breast cancer cells, ESR1 and ER46 co-localize with EGFR and ERBB2 in lipid rafts,71 and in ESR1-negative cells a positive-feedback loop involving ER36 and EGFR promotes malignant growth.72 Differential perturbations of coactivity among the estrogen and EGF family receptors might contribute to the many different breast cancer subtypes described using whole-genome transcriptomic approaches, which often appear to be disconnected from the activity of the traditional clinical markers.73