Method of selection for treatment of subjects at risk of invasive breast cancer

Abstract

The present disclosure provides compositions and methods for the treatment of subjects having a risk of invasive breast cancer. In some embodiments, these aspects allow for the pairing of the proper treatment option for the particular subject. In some embodiments, this allows for identifying subjects who, while at risk for invasive breast cancer, will not normally respond to radiation therapy, and can instead receive an alternative therapy, such as a HER2 antibody.

1 . A method of treating a subject, the method comprising:
 identifying a subject with DCIS that has an elevated level of activity in a k-ras pathway; and   administering an aggressive breast cancer therapy to the subject.   
     
     
         2 . The method of  claim 1 , wherein the k-ras pathway is elevated if there is an elevated level of at least one of: K-ras, RAF, MAPK, MEK, ETS or SIAH, and wherein the subject is HER2 positive. 
     
     
         3 . A method of treating a subject, the method comprising:
 identifying a subject with DCIS, that is HER2 positive and SIAH2 positive; and   administering an aggressive breast cancer therapy to the subject, wherein the aggressive breast cancer therapy is aggressive radiation therapy or aggressive non-radiation therapy.   
     
     
         4 . (canceled) 
     
     
         5 . A method of identifying a subject for an aggressive cancer therapy, the method comprising:
 identifying a subject with DCIS at an elevated risk of invasive breast cancer; and   determining if the subject is HER2 and SIAH2 positive,   wherein if the subject is HER2 and SIAH2 positive, administering an aggressive therapy to the subject,   wherein the aggressive therapy:
 a) is not radiation therapy; 
 b) is aggressive radiation therapy; 
 c) is chemotherapy; 
 d) is a therapy that comprises an anti-HER2 antibody; or 
 e) is selected from the group consisting of: an antibody to HER2 or Trastuzumab. 
   
     
     
         6 . (canceled) 
     
     
         7 . A method for treating a subject, said method comprising:
 providing a DCIS sample from a subject;   analyzing the DCIS sample for a level of at least PR and HER2, and at least either:
 a) analyzing the sample for at least SIAH2, or 
 b) analyzing the sample for at least FOXA1; and 
   providing a prognosis based upon at least PR, HER2 and SIAH2 or based upon at least PR and FOXA1,   wherein if the sample is PR positive, further analyzing the sample for a level of COX2, wherein COX2 positive with at least FOXA1 positive indicates a high risk of invasive breast cancer,   determining if the subject is HER2 positive; and   administering an aggressive therapy to the subject if the subject is HER2 positive,   wherein the aggressive therapy is more aggressive than the standard of care therapy.   
     
     
         8 . The method of  claim 3 , further comprising:
 analyzing the sample for a level of Ki67; and   identifying the subject as having an elevated risk of invasive breast cancer based on a determination that there is a high level of Ki67 in the sample.   
     
     
         9 . The method of  claim 1 , wherein the aggressive therapy comprises an anti-HER2 antibody. 
     
     
         10 . The method of  claim 9 , wherein the antibody is Trastuzumab. 
     
     
         11 . A method of providing a benefit of radiation therapy, the method comprising:
 identifying a subject with DCIS at elevated risk of invasive breast cancer; and   administering radiation therapy to the subject if the subject is HER2 negative and administering aggressive radiation therapy or aggressive non-radiation therapy to the subject if the subject is HER2 positive.   
     
     
         12 .- 17 . (canceled) 
     
     
         18 . The method of  claim 5 , wherein the subject is high risk if they are PR positive and there is a very high level of FOXA1. 
     
     
         19 . The method of  claim 5 , wherein if a sample is PR positive, then further analyzing the sample for Ki67, size, or both Ki67 and size. 
     
     
         20 . The method of  claim 5 , wherein if the sample is PR positive, and wherein when FOXA1 negative, further analyzing the sample for a level of Ki67, size, or a level of Ki67 and size, wherein Ki67 positive, a size larger than 5 mm of DCIS, or both, indicates high risk. 
     
     
         21 . The method of  claim 5 , further comprising analyzing for p16, COX2, and Ki67. 
     
     
         22 . The method of  claim 5 , wherein analysis of each marker is carried out in parallel with each other. 
     
     
         23 . (canceled) 
     
     
         24 . The method of  claim 5 , wherein PR analysis occurs first and any further analysis depends upon the result of the PR analysis. 
     
     
         25 . The method of  claim 5 , wherein no additional markers are looked at to determine the therapy. 
     
     
         26 . The method of  claim 11 , comprising:
 analyzing the sample for a level of Ki67; and   identifying the subject as having the elevated risk of invasive breast cancer based on a determination that there is a high level of Ki67 in the sample.   
     
     
         27 . A kit comprising:
 a first detectable binding agent specific for HER2; and   a second detectable binding agent specific for SIAH2.   
     
     
         28 . The kit of  claim 27 , further comprising one or more third detectable binding agents specific for one or more of FOXA1, PR, Ki67, and p16. 
     
     
         29 . The kit of  claim 27 , wherein the first and second detectable binding agents comprise a nucleic acid probe or an antibody.