While several of the investigated pathway proteins including ERK1/2, STAT3, CREB, p70 S6 kinase, and IkBa did appear to be regulated independent from the level of HER2 expression and were not affected by TKI-mediated HER receptor blockade, JNK and STAT5A/B clearly showed differential response against the HER-TKIs, which directly correlated with the sensitivity of the breast cancer cells against these TKIs. The gene discussed is CREB1; the disease is breast cancer.