In agreement, we find that the hormone receptor-positive breast cancer cell line MCF-7, which we score HER2-negative, has weak to moderate levels of HER2 mRNA and protein [27], and addition of the HER3/HER4 ligand heregulin 1β clearly abrogated the inhibitory effect of antiestrogen treatment equally well in both wild-type and HER2/HER3 overexpressing MCF-7 cells – suggesting that activation of even a low level of HER2 via dimerization of ligand-activated HER3 may suffice to protect against antiestrogen therapy [27]. This evidence concerns the gene ERBB4 and breast carcinoma.