ER and PI3K Independently Modulate Endocrine Resistance in ER-Positive Breast Cancer

Endocrine therapy-resistant estrogen receptor-positive (ER+) breast cancer is the most common cause of breast cancer death. Miller and colleagues demonstrate that ligand-independent ER activity promotes the growth of breast cancer cells through CDK4/E2F. As an independent event, the phosphatidylinositol 3-kinase (PI3K) pathway is also upregulated in endocrine therapy-resistant cells. Promising preclinical evidence by several groups for the combination of an inhibitor of ligand-independent ER, fulvestrant, with PI3K inhibition, has led to the activation of trials evaluating this concept. Cancer Discovery; 1(4): 287-8. (C) 2011 AACR.