Since trastuzumab induces the release of endogenous heregulin [23] and this could induce γ-secretase-mediated HER4 cleavage and nuclear localisation [26], we utilized γ-secretase inhibitor and showed that it decreased m80 and nuclear HER4 translocation in HER2 positive breast cancer cells when combined with trastuzumab. Here, ERBB2 is linked to breast carcinoma.