Zheng H, et al. - In breast cancer patients, researchers explored the association between serum human epidermal growth factor receptor-2 (HER-2) extracellular domain (ECD) shedding and tissue HER-2 status in this retrospective observational study. From Fudan University Shanghai Cancer Center, they enrolled a total of 545 unselected breast cancer patients in this study. Outcomes revealed no complete matching of serum HER-2 ECD with tissue HER-2 status due to the differential expression of alpha-secretase activity of a disintegrin and metalloproteinase 10 (ADAM10). The poorer prognosis was evident in correlation with increased HER-2 ECD shedding due to overexpression of ADAM10. They suggest the potential therapeutic benefit of inhibiting ADAM10 activity for this very aggressive tumor subgroup.