Horimoto Y, Terao T, Tsutsumi Y, et al. - In order to determined the reasons for more frequent overexpression of human epidermal growth factor receptor 2 (HER2) protein in ductal carcinoma in situ (DCIS) than in invasive ductal carcinoma (IDC), researchers sought to test their hypothesis based on the high frequency of estrogen receptor-positive (ER+) and HER2-positive (HER2+) DCIS, that this tumor type overexpresses HER2 protein without gene amplification. They retrospectively investigated 71 ER(+)HER2(+) DCIS, surgically removed during the 2007 to 2017 period for the HER2/neu gene status, using fluorescence in situ hybridization. In addition, they examined 86 pT1mi/1a IDC with predominantly in situ disease to compare HER2 protein expressions between in situ and invasive components of individual tumors. Analysis of public microarray data of mRNA was done to illustrate biological differences among DCIS with various combinations of ER and HER2 protein expressions. Outcomes support that HER2 protein is frequently overexpressed without gene amplification in ER(+) and HER2 protein-overexpressing DCIS, especially ER-high tumors. Data may render novel insights for understanding the biology of DCIS.