Moreover, these observations also suggest that sensitivity of PTEN deficient breast cancer cells to PI3K pathway inhibitors may be dependent on epistatic interactions between PI3K pathway genes and genes from other signaling pathways such as the MAPK pathway, as well as the release of negative feedback loops and the node targeted by pharmacologic inhibition (Efeyan and Sabatini, 2010; Zhang and Yu, 2010). This evidence concerns the gene PIK3CD and breast cancer.