Methods for prognosis and monitoring cancer therapy

Abstract

The present invention also relates to biomarkers and the use of biomarkers for the prediction and prognosis of cancer as well as the use of biomarkers to monitor the efficacy of cancer treatment. Specifically, this invention relates to the use of HER-2, EGFR, VEGF, u-PA, p-PAI-1, and soluble forms thereof, as biomarkers for cancer, especially for subjects treated with sorafenib.

1 .- 3 . (canceled) 
     
     
         4 . A method for treating a patient with sorafenib for breast cancer after initial therapeutic treatments, based on the patient's response during the course of therapeutic treatment, said method comprising treating the patient with the same amount of sorafenib, a different amount of sorafenib, adding an additional therapeutic treatment or ceasing treatment with sorafenib, in view of the effectiveness of the treatment with sorafenib as determined by comparing the level of expression of one or more biomarker(s) selected from the group consisting of HER-2, EGFR, and soluble forms thereof, in at least a second biological sample with the level of expression of the one or more biomarker(s) in a first biological sample; wherein
 (a) the first biological sample is taken from the patient prior to treatment with sorafenib; and   (b) the at least second biological sample is taken from the patient subsequent to the initial treatment with sorafenib; and   
       wherein a change in the level of expression of the one or more biomarker(s) in the second biological sample compared to the level of expression of the one or more biomarker(s) in the first biological sample as compared to statistically valid changes in the baseline level of expression of the biomarker(s) in other patients showing an effective response to sorafenib indicates the effectiveness or lack thereof of the treatment with sorafenib, and
 wherein 
 higher levels of expression of HER-2 or a soluble form thereof indicates a poorer response and/or prognosis, and 
 higher levels of expression of EGFR or a soluble form thereof indicates a better response and/or prognosis. 
 
     
     
         5 . A method of therapeutic treatment with sorafenib for a subject having a breast cancer and having a high baseline level of soluble EGFR, said method comprising administering further treatment based on a prediction of therapeutic outcome; wherein said prediction is based on a statistically valid comparison of
 the change in the level of expression of soluble EGFR in said subject in response to prior treatment with sorafenib, with changes in levels of expression from the subject's baseline of soluble EGFR, to   the change in level of expression of soluble EGFR before and after treatment with sorafenib in other breast cancer patients having a high baseline level of soluble EGFR and having a clinically beneficial response to sorafenib, to predict the clinical benefit of continuing the administration of effective amounts of sorafenib;   
       wherein changes in levels of expression of soluble EGFR are determined by:
 (a) measuring the level of expression of soluble EGFR in said subject after administration of sorafenib, 
 (b) determining the change in the level of expression of soluble EGFR in said subject after administration of sorafenib, from the high baseline levels of soluble EGFR; 
 
       wherein statistically valid changes from baseline expression levels of previously treated patients having a clinically beneficial response are used to predict clinical benefit of further treatment, wherein said further treatment comprises administering to the subject the same amount of sorafenib, a different amount of sorafenib, adding an additional therapeutic treatment or ceasing treatment with sorafenib, and 
       wherein higher levels of expression of soluble EGFR indicate a better response and/or prognosis.