Taken together, these results demonstrate that the residual expression of p4EBP1 in the post-treatment, which is mediated by PIK3CA mutations, would attenuate the antiproliferative effects of lapatinib in both ER+/HER2+ and ER−/HER2+ breast cancer cell lines, supporting the clinical results demonstrating relatively poor prognosis in patients with HER2+ breast cancer patients with active mutations in the PI3K pathway regardless of the status of ER expression (Fig. 1). This evidence concerns the gene PIK3CA and breast cancer.