PIK3CA and breast cancer: Furthermore, to confirm that constitutive activation of PI3K signaling caused by PIK3CA-mutations attenuates the antiproliferative effects of HER2 inhibition regardless of ER status, we tested four additional ER−/HER2+ breast cancer cell lines: SK-BR-3 cells and ZR-75-30 cells (PIK3CA-wt/ER−/HER2+), and UACC893 cells and HCC1954 cells (both PIK3CA-mut [H1047R]/ER−/HER2+) (Fig. 3c).