We observed that ERK/MAPK, STAT3 and CREB were inhibited in both sensitive and resistant breast cancer cell lines, whereas JNK and STAT5A/B were only inhibited in the sensitive cell line SKBR3, which suggests that in addition to hyperactivity of HER and of downstream PI3K signaling [24] these two parameters also contribute to the development of resistance of breast cancer cells against HER-TKIs. Here, CREB1 is linked to breast cancer.