Zheng H, et al. - A total of 545 unselected breast cancer patients from Fudan University Shanghai Cancer Center were analyzed to assess the relationship between serum HER-2 ECD shedding and tissue HER-2 status in cases with breast cancer. Researchers observed low levels of HER-2 extracellular domain (ECD) shedding (<15 ng/mL) in serum among 36.9% of subjects with tissue HER-2 overexpression. Using tumor tissues and cell lines, they explained an association of HER-2 ECD shedding with protein expression and alpha-secretase activity of a disintegrin as well as metalloproteinase 10 (ADAM10). Subjects with serum HER-2 ECD above 15 ng/mL were recorded with lower progression-free survival as compared to those with serum HER-2 ECD <15 ng/mL. Therefore, serum HER-2 ECD could be regarded as a biomarker to distinguish the subgroup of poorer outcome among HER-2 overexpression.