Gene expression profiles to predict breast cancer outcomes

Abstract

Methods for classifying and for evaluating the prognosis of a subject having breast cancer are provided. The methods include prediction of breast cancer subtype using a supervised algorithm trained to stratify subjects on the basis of breast cancer intrinsic subtype. The prediction model is based on the gene expression profile of the intrinsic genes listed in Table 1. This prediction model can be used to accurately predict the intrinsic subtype of a subject diagnosed with or suspected of having breast cancer. Further provided are compositions and methods for predicting outcome or response to therapy of a subject diagnosed with or suspected of having breast cancer. These methods are useful for guiding or determining treatment options for a subject afflicted with breast cancer. Methods of the invention further include means for evaluating gene expression profiles, including microarrays and quantitative polymerase chain reaction assays, as well as kits comprising reagents for practicing the methods of the invention.

What is claimed is: 
     
         1 . A method, comprising
 (a) providing a biological sample of a subject, and   (b) assaying said biological sample for expression products of a plurality of genes,   wherein said plurality of genes comprise at least 40 genes selected from Table 1, and   wherein said assaying comprises use of probes having sequences complementary to said expression products of said plurality of genes.   
     
     
         2 . The method of  claim 1 , wherein said subject has been diagnosed with cancer. 
     
     
         3 . The method of  claim 2 , wherein said cancer is breast cancer. 
     
     
         4 . The method of  claim 3 , wherein said breast cancer has been previously identified as a luminal A intrinsic subtype. 
     
     
         5 . The method of  claim 3 , wherein said breast cancer has been previously identified as a luminal B intrinsic subtype. 
     
     
         6 . The method of  claim 3 , wherein said breast cancer has been previously identified as a basal-like intrinsic subtype. 
     
     
         7 . The method of  claim 3 , wherein said breast cancer has been previously identified as a HER2 enriched intrinsic subtype. 
     
     
         8 . The method of  claim 1 , wherein said subject is undergoing a breast cancer therapy. 
     
     
         9 . The method of  claim 8 , wherein said breast cancer therapy is an endocrine therapy. 
     
     
         10 . The method of  claim 9 , wherein said endocrine therapy is a neoadjuvant endocrine therapy. 
     
     
         11 . The method of  claim 8 , wherein said breast cancer therapy is a chemotherapy. 
     
     
         12 . The method of  claim 1 , wherein said assaying comprises (i) using said probes to selectively bind to said expression products to yield an enriched sample, (ii) using said enriched sample to generate a plurality of deoxyribonucleic acid (DNA) molecules, and (iii) sequencing said plurality of DNA molecules. 
     
     
         13 . The method of  claim 1 , wherein said plurality of genes comprise at least 41 genes selected from Table 1. 
     
     
         14 . The method of  claim 1 , wherein said plurality of genes comprise at least 42 genes selected from Table 1. 
     
     
         15 . The method of  claim 1 , wherein said plurality of genes comprise at least 43 genes selected from Table 1. 
     
     
         16 . The method of  claim 1 , wherein said plurality of genes comprise at least 44 genes selected from Table 1. 
     
     
         17 . The method of  claim 1 , wherein said plurality of genes comprise at least 45 genes selected from Table 1. 
     
     
         18 . The method of  claim 1 , wherein said plurality of genes comprise at least 46 genes selected from Table 1. 
     
     
         19 . The method of  claim 1 , wherein said plurality of genes comprise at least 47 genes selected from Table 1. 
     
     
         20 . The method of  claim 1 , wherein said plurality of genes comprise at least 48 genes selected from Table 1.