Compositions, kits, and methods for identification, assessment, prevention, and therapy of breast cancer

Abstract

The invention relates to nucleic acid molecules and proteins associated with breast cancer. Compositions, kits, and methods for detecting, characterizing, preventing, and treating human breast cancers are provided.

1 . A method of assessing whether a patient is afflicted with breast cancer, the method comprising:
 a) determining the level of expression of a marker in a patient sample, wherein the marker is selected from the group consisting of the markers listed in Table 1 and the markers listed in Table 2;   b) determining the level of expression of the marker in a control sample; and   c) comparing the level of expression of the marker in the patient sample and the level of expression of the marker in the control sample,   wherein a difference between the level of expression of the marker in the patient sample as compared to the level of expression of the marker in the control sample is an indication that the patient is afflicted with breast cancer.   
     
     
         2 . The method of  claim 1 , wherein the control sample comprises breast cells from the patient which are non-cancerous. 
     
     
         3 . The method of  claim 1 , wherein the level of expression of the marker in the control sample is predetermined using an average of the levels of expression of the marker in samples from a population of subjects having indolent breast tumors or no breast tumors. 
     
     
         4 . The method of  claim 1 , wherein the marker comprises a transcribed polynucleotide or portion thereof. 
     
     
         5 . The method of  claim 1 , wherein the patient sample comprises cells obtained from the patient. 
     
     
         6 . The method of  claim 1 , wherein the patient sample comprises a fluid selected from the group consisting of blood fluid, lymph, cystic fluid, nipple aspirates, and fluid collected from a lump biopsy. 
     
     
         7 . The method of  claim 1 , wherein the level of expression of the marker in the patient sample is assessed by detecting the presence of a marker protein in the sample. 
     
     
         8 . The method of  claim 7 , wherein the presence of the marker protein is detected using a reagent which specifically binds with the protein. 
     
     
         9 . The method of  claim 8 , wherein the reagent is selected from the group consisting of an antibody, an antibody derivative, an antigen-binding antibody fragment, and a non-antibody peptide which specifically binds the protein. 
     
     
         10 . The method of  claim 9 , wherein the antibody or antigen-binding antibody fragment is a monoclonal antibody or antigen-binding fragment thereof, or a polyclonal antibody or antigen-binding fragment thereof. 
     
     
         11 . The method of  claim 9 , wherein the antibody or antigen-binding antibody fragment is labelled. 
     
     
         12 . The method of  claim 11 , wherein the antibody or antigen-binding antibody fragment is radio-labelled, biotin-labelled, chromophore labelled, fluorophore labelled, or enzyme labelled. 
     
     
         13 . The method of  claim 1 , wherein the level of expression of the marker in the patient sample is assessed by detecting the presence in the patient sample of a transcribed polynucleotide or portion thereof, corresponding to a nucleic acid marker. 
     
     
         14 . The method of  claim 13 , wherein the transcribed polynucleotide is a mRNA or a cDNA. 
     
     
         15 . The method of  claim 13 , wherein the step of detecting a transcribed polynucleotide further comprises amplifying the transcribed polynucleotide. 
     
     
         16 . The method of  claim 1 , wherein the level of expression of the marker in the patient sample is assessed by detecting the presence in the patient sample of a transcribed polynucleotide which anneals with a nucleic acid marker or a portion thereof under stringent hybridization conditions. 
     
     
         17 . The method of  claim 1 , wherein the level of expression of the marker in the patient sample differs from the level of expression of the marker in the control sample by a factor selected from the group consisting of: a factor of at least about 2, a factor of at least about 3, a factor of at least about 4, and a factor of at least about 5. 
     
     
         18 . The method of  claim 1 , wherein the level of expression of the marker in the patient sample is assessed using a technique selected from the group consisting of: Northern hybridization, polymerase chain reaction analysis, RT-PCR, probe array and in situ hybridization. 
     
     
         19 . A method of assessing whether a patient is afflicted with breast cancer, the method comprising:
 a) determining the level of expression in a patient sample of at least two markers independently selected from the markers listed in Table 1 and Table 2;   b) determining the level of expression of each of the markers in a control sample; and   c) comparing the level of expression of the marker in the patient sample and the level of expression of the marker in the control sample;   wherein a difference in the level of expression of more than one of the markers in the patient sample as compared to the corresponding level of expression of the markers in the control sample, is an indication that the patient is afflicted with breast cancer.   
     
     
         20 . The method of  claim 19 , wherein the level of expression of at least three markers or at least five markers is determined. 
     
     
         21 . A method for assessing whether a patient has breast cancer that has metastasized or is likely to metastasize, comprising:
 a) determining the level of expression of a marker in a patient sample, wherein the marker is selected from the markers listed in Table 2,   b) determining the level of expression of the marker in a control sample, and   c) comparing the level of expression of the marker in the patient sample and the level of expression of the marker in the control sample;   wherein a higher level of expression in the patient sample as compared to the level of expression of the marker in the control sample is an indication that the breast cancer has metastasized or is likely to metastasize.   
     
     
         22 . The method of  claim 21 , wherein the assessment is indicative of whether the patient is afflicted with metastatic breast cancer that has metastasized to lymph nodes, or is likely to metastasize to lymph nodes. 
     
     
         23 . A method for predicting the clinical outcome of a breast cancer patient, the method comprising:
 a) determining the level of expression of a marker in a patient sample, wherein the marker is selected from the markers listed in Table 2,   b) determining the level of expression of the marker in a sample from a control subject having a good clinical outcome; and   c) comparing the level of expression of the marker in the patient sample and the level of expression of the marker in the sample from the control subject;   wherein a higher level of expression of the marker in the patient sample as compared to the level of expression of the marker in the sample from the control subject is an indication that the patient has a poor clinical outcome.   
     
     
         24 . A method for monitoring the progression of breast cancer in a patient, the method comprising:
 a) determining the level of expression of a marker in a patient sample from a first point in time, wherein the marker is selected from the group consisting of the markers listed in Table 1 and the markers listed in Table 2;   b) determining the level of expression of the marker in a sample from the patient at a subsequent point in time; and   c) comparing the level of expression detected in steps a) and b), thereby monitoring the progression of breast cancer in the patient,   wherein a change in the level of expression of the marker is indicative of either progression or regression of breast cancer.   
     
     
         25 . The method of  claim 24 , wherein the patient has undergone surgery to remove a tumor between the first point in time and the subsequent point in time. 
     
     
         26 . The method of  claim 24 , wherein the first and second samples are portions of a single sample obtained from the patient, or portions of pooled samples obtained from the patient. 
     
     
         27 . A method of assessing the efficacy of a therapy for inhibiting breast cancer in a patient, the method comprising:
 a) determining the level of expression of a marker in a first sample obtained from the patient prior to administering at least a portion of the therapy to the patient, wherein the marker is selected from the group consisting of the markers listed in Table 1 and the markers listed in Table 2,   b) determining the level of expression of the marker in a second sample obtained from the patient subsequent to administering the portion of the therapy;   c) comparing the level of expression of the marker in the first sample as compared to the level of expression of the marker in the second sample; and   d) determining that the therapy is efficacious for inhibiting breast cancer in the patient when there is a lower level of expression of the marker in the second sample, relative to the first sample.   
     
     
         28 . A kit for assessing whether a patient is afflicted with breast cancer, the kit comprising reagents for assessing expression at least one marker selected from the group consisting of the markers listed in Table 1 and the markers listed in Table 2.