Background: HER2 belongs to the epidermal growth factor (EGF) tyrosine kinase receptor family. HER2 is unique for both its functional characteristics as an orphan receptor that heterodimerizes with other tyrosine kinase receptors (TKIs) and its high oncogenic potential. The HER2 gene is amplified in 15–20% of BCs, resulting in markedly increased HER2 protein content on the cell surface and enhanced signal transduction through HER2 heterodimers. Low HER2 expression referred to IHC+1 (Incomplete membrane staining that is faint / barely perceptible and in >10% of tumor cells) and IHC +2(weak to moderate complete membrane staining>10% of tumor cells with negative ISH test). To date, several molecular mechanisms of HER2 overexpression in BC have been described, of these, amplification of the HER2 gene (also called erbB-2 and neu) is the most common mechanism. BCs can have up to 25–50 copies of the HER2 gene and up to 40–100-fold increases in HER2 protein expression, resulting in up to 2 million receptors expressed at the tumor cell surface