Methods and compositions for evaluating breast cancer prognosis

Abstract

Methods and compositions for evaluating the prognosis of a breast cancer patient, particularly an early-stage breast cancer patient, are provided. The methods of the invention comprise detecting expression of at least one, more particularly at least two, biomarker(s) in a body sample, wherein overexpression of the biomarker or a combination of biomarkers is indicative of breast cancer prognosis. In some embodiments, the body sample is a breast tissue sample, particularly a primary breast tumor sample. The biomarkers of the invention are proteins and/or genes whose overexpression is indicative of either a good or bad cancer prognosis. Biomarkers of interest include proteins and genes involved in cell cycle regulation, DNA replication, transcription, signal transduction, cell proliferation, invasion, proteolysis, or metastasis. In some aspects of the invention, overexpression of a biomarker of interest is detected at the protein level using biomarker-specific antibodies or at the nucleic acid level using nucleic acid hybridization techniques.

1 . A method for evaluating the prognosis of a breast cancer patient, said method comprising detecting overexpression of at least one biomarker in a sample from said patient, wherein said biomarker is selected from the group consisting of SLPI, p21ras, MUC-1, DARPP-32, phospho-p27, src, MGC 14832, myc, TGFβ-3, SERHL, E2F1, PDGFRα, NDRG-1, MCM2, PSMB9, and MCM6, wherein overexpression of said biomarker is indicative of prognosis, and thereby evaluating the prognosis of said breast cancer patient. 
     
     
         2 . A method for evaluating the prognosis of a breast cancer patient, said method comprising:
 a) obtaining a sample from said patient;   b) contacting said sample with at least one antibody, wherein said antibody specifically binds to a biomarker protein, wherein said biomarker protein is selected from the group consisting of SLPI, p21ras, MUC-1, DARPP-32, phospho-p27, src, MGC 14832, myc, TGFβ-3, SERHL, E2F1, PDGFRα, NDRG-1, MCM2, PSMB9, and MCM6;   c) detecting binding of said antibody to said biomarker protein;   d) determining if said biomarker protein is overexpressed in said sample, wherein overexpression of said biomarker protein is indicative of a poor prognosis; and,   e) thereby evaluating the prognosis of said breast cancer patient.   
     
     
         3 . The method of  claim 2 , wherein said biomarkers are selected from the group consisting of SLPI, p21ras, MUC-1, DARPP-32, phospho-p27, src, MGC 14832, myc, TGFβ-3, SERHL, E2F1, PDGFRα, NDRG-1, MCM2, PSMB9, and MCM6. 
     
     
         4 . A kit comprising at least two antibodies, wherein each of said antibodies specifically binds to a distinct biomarker protein that is indicative of poor prognosis of a breast cancer patient, and wherein the biomarker proteins are selected from the group consisting of SLPI, p21ras, MUC-1, DARPP-32, phospho-p27, src, MGC 14832, myc, TGFβ-3, SERHL, E2F1, PDGFRα, NDRG-1, MCM2, PSMB9, and MCM6. 
     
     
         5 . The kit of  claim 4 , wherein said biomarker proteins are selected from the group consisting of E2F1, SLPI, MUC-1, src, p21ras, and PSMB9. 
     
     
         6 . The kit of  claim 4 , wherein said kit further comprises chemicals for the detection of antibody binding to said biomarker protein. 
     
     
         7 . The kit of  claim 4 , wherein said kit is used with a commercial antibody binding detection system. 
     
     
         8 . The kit of  claim 4 , wherein said kit further comprises a positive control sample. 
     
     
         9 . The kit of  claim 4 , wherein said kit further comprises instructions for use.