ERBB2 and breast cancer: Simultaneously, given that efficacy of trastuzumab appears to relate directly to its ability to drastically reduce the fraction of ALDH-positive cells in HER2+ BC cell populations (i.e., CSC populations defined by high ALDH express the highest HER2 levels and remain exquisitely sensitive to trastuzumab treatment, whereas HER2+ BC cell populations exhibiting primary resistance to trastuzumab maintain an intact population of ALDH+ cells following trastuzumab treatment [58]), HER2e/cHER2+ and luminal B/cHER2+ BC will be the mixed phenotype which will benefit greatest from trastuzumab (Figure 2).