The process of angiogenesis plays a critical role in breast cancer growth and metastasis. Recently, Avastin (an antibody against VEGF-vascular endothelial growth factor) has emerged as the first successful demonstration of anti-angiogenic therapy in advanced cancer. In breast cancer, Herceptin (an antibody against the Her-2 oncogene that also inhibits angiogenesis) has recently been proven to be an effective treatment against metastatic cases. The success of Herceptin is partially attributed to the predictive value of the degree of oncogene expression in the breast cancer tissue. On the other hand, at this point, there is no reliable marker that would help predict or monitor a clinical response to anti-angiogenic therapy. We hypothesize that a comprehensive profile of known and novel markers can predict/monitor the success of anti-angiogenic treatment of breast cancer. We believe that the identification of reliable markers permits more effective selection of the correct treatment regimen for the individual patient. In this grant application, we propose a pilot project to measure the effect of Avastin and Herceptin administration on the several angiogenic and breast cancer biomarkers. The serum from responders will be compared to those from non-responders to determine the identity of those markers that would predict therapeutic success.
The specific aims are as follows:
Aim #1 : To collect blood samples from patients in the UCLA breast cancer Avastin and Herceptin clinical trial. These specimens will be collected prior to initiation of therapy, and every month thereafter.
Aim #2 : To test the hypothesis that a successful response to Avastin and Herceptin administration will result in the modulation of specific angiogenic and breast cancer biomarkers. The levels of multiple angiogenic factors and inhibitors as well as breast tumor markers will be correlated with the patients' clinical response and outcome.
Aim #3 : To identify potential protein biomarkers in individual responder serum samples using isotopic labeling and mass spectrometry. The serum proteome database will be used for the comparatively rapid analysis of serum samples from responder individuals. Relative levels of peptides in each sample will be determined by comparison with an isotopically labeled internal standard .
