HER2/HER3, Breast Cancer

HER2 overexpression/amplification is linked with poor prognosis in early breast cancer. Co-expression of HER2 and HER3 is associated with endocrine and chemotherapy resistance, driven not simply by expression but by signaling via HER2:HER3 or HER2:HER2 dimers. Proximity ligation assays (PLAs) detect protein–protein complexes at a single-molecule level and allow study of signaling pathways in situ. PLA has been shown to successfully and reproducibly detect HER2:HER2 and HER2:HER3 protein complexes in vivo. It has also been shown that a significant association (P<0.00001) was identified between HER2 homodimerization and HER2 gene amplification, where high levels of HER2:HER2 dimers were significantly associated with reduced relapse free and overall survival.