Subsequently, the ECD of the Her2/neu protein was shown to be proteolytically cleaved by metalloproteases from the surface of the cells and released in the supernatants of the culture media in vitro and also detectable in the circulation of patients with breast cancer (Zabrecky et al, 1991; Pupa et al, 1993; Wu et al, 1995). This evidence concerns the gene ERBB2 and breast cancer.