HER2, in particular, activates numerous Rac GEFs including P-Rex1, VAV2 and DOCK1 resulting in Rac activation in breast cancer.28, 29, 30 Constitutively, active Rac1 variants have also been identified in breast cancers such as the splice variant Rac1b18, 41 and activating mutational variants,42 suggesting that Rac1 signaling is a major component in breast cancer. This evidence concerns the gene ERBB2 and breast carcinoma.