Does the PI3K Pathway Play a Role in Basal Breast Cancer?

Many cell kinases exert their proliferative and pro-survival effects through activation of the phosphatidylinositol 3-kinase (PI3K)-Akt pathway. Basal-like breast cancer is a subtype that can be identified by molecular analysis and often includes tumors lacking expression of estrogen receptor/progesterone receptor or human epidermal growth factor receptor, also known as triple-negative breast cancers. Triple-negative cancers comprise < 20% of all breast cancers and have no obvious mechanism driving proliferation, yet these tumors demonstrate higher levels of Akt activation compared with non–triple-negative breast cancers. This suggests a possible role for targeting the PI3K pathway for the treatment of this subset of aggressive cancers. Most clinical trials which have attempted targeting the PI3K/Akt pathway in triple-negative breast cancer have involved the use of EGFR inhibitors with limited success. Novel agents targeting PI3K are under development in early-phase clinical trials and may demonstrate benefit in combination with chemotherapy or other targeted agents such as mitogen-activated protein kinase inhibitors for the treatment of triple-negative or basal-like breast cancer.