Abstract 391: Serum ferritin predicts response to trastuzumab and is a biomarker for breast and pancreatic cancers: A potential novel inflammatory effector mechanism

Inflammation plays a critical role in cancer. However, it is still unclear what inflammatory effector mechanisms, if any, are directly responsible for enhancing tumorigenesis. Serum ferritin is an acute-phase protein that is elevated in multiple cancer types including breast cancer. However due to the prevailing paradigm on ferritin as a ‘house-keeping’ iron storage protein, no further investigation of the functional significance of serum ferritin or its clinical utility in cancer has been made thus far. In light of recent advances in iron and ferritin biology, we hypothesized that the elevation in serum ferritin represents an inflammatory effector mechanism that is actively and directly enhancing tumorigenesis, and thus it can be used to predict clinical outcome. Herein we provide data that extracellular ferritin stimulates proliferation of breast cancer cells and activates AKT signaling through an iron-independent mechanism - a novel function for this traditional iron storage protein. With this novel mechanism in mind, we made clinical predictions about the ability of serum ferritin to predict response to the anti-HER2/neu antibody trastuzumab. Higher pretreatment serum ferritin was significant on a continuous basis for predicting reduced Overall Survival (OS, p