Methods for treating, preventing and predicting risk of developing breast cancer

Abstract

Methods for treating, preventing and predicting a subject's risk of developing breast cancer are provided. In one aspect, a method of predicting a subject's risk of developing breast cancer is provided, wherein the method includes: (a) determining the frequency in a breast tissue sample of CD44+, CD24− breast epithelial cells, and (b) predicting that the subject has a relatively elevated risk of developing breast cancer if the frequency of CD44+, CD24− breast epithelial cells is decreased compared to a first control frequency of CD44+, CD24− breast epithelial cells; or (c) predicting that the subject has a relatively reduced risk of developing breast cancer if the frequency of CD44+ breast epithelial cells is increased compared to a second control frequency of CD44+, CD24− breast epithelial cells.

1 . A method of predicting a subject's risk of developing breast cancer, wherein the method comprises:
 (a) determining, in a breast tissue sample from a subject, the frequency of CD44+, CD24− breast epithelial cells or the frequency of CD44+ breast epithelial cells with an assay that comprises the use of one or both of an antibody that binds specifically to CD44 and an antibody that binds specifically to CD24, and   (b) predicting that the subject has a relatively elevated risk of developing breast cancer if the frequency of CD44+, CD24− breast epithelial cells is decreased compared to a first control frequency of CD44+, CD24− breast epithelial cells; or   predicting that the subject has a relatively reduced risk of developing breast cancer if the frequency of CD44+ breast epithelial cells is increased compared to a second control frequency of CD44+, CD24− breast epithelial cells.   
     
     
         2 . The method of  claim 1 , further comprising determining the frequency of CD24+ breast epithelial cells. 
     
     
         3 . The method of  claim 2 , wherein step (b) comprises:
 predicting that the subject has a relatively elevated risk of developing breast cancer if: (i) the frequency of CD44+, CD24− breast epithelial cells is decreased compared to the first control frequency of CD44+, CD24− breast epithelial cells, and (ii) the frequency of CD24+ breast epithelial cells is increased compared to a first control frequency of CD24+ breast epithelial cells; or   predicting that the subject has a relatively reduced risk of developing breast cancer if: (i) the frequency of CD44+_breast epithelial cells is increased compared to the second control frequency of CD44+, CD24− breast epithelial cells, and (ii) the frequency of CD24+ breast epithelial cells is decreased compared to a second control frequency of CD24+ breast epithelial cells.   
     
     
         4 . The method of  claim 2 , wherein step (b) comprises:
 predicting that the subject has a relatively elevated risk of developing breast cancer if the frequency of CD24+ breast epithelial cells is greater than the frequency of CD44+, CD24-breast epithelial cells in the sample; or   predicting that the subject has a relatively reduced risk of developing breast cancer if the frequency of CD24+ breast epithelial cells is equal to or less than the frequency of CD44+, CD24− breast epithelial cells in the sample.   
     
     
         5 . The method of  claim 1 , wherein the subject is in need of such predicting. 
     
     
         6 . A method of predicting a subject's risk of developing breast cancer, wherein the method comprises:
 (a) determining the frequency in a breast tissue sample of cells of one or more types selected from the group consisting of p27+ breast epithelial cells, Sox17+ breast epithelial cells, Cox2+ breast epithelial cells, Ki67+ breast epithelial cells, ER+, p27+ breast epithelial cells, ER+, Sox17+ breast epithelial cells, ER+, Cox2+ breast epithelial cells, ER+, Ki67+ breast epithelial cells; androgen-receptor-positive (AR+), p27+ breast epithelial cells, AR+, Sox17+ breast epithelial cells, AR+, Cox2+ breast epithelial cells, and AR+, Ki67+ breast epithelial cells with an assay that comprises the use of one or more antibodies selected from the group consisting of: an antibody that binds specifically to p27, an antibody that binds specifically to Sox17, an antibody that bind specifically to Cox2, an antibody that binds specifically to Ki67, an antibody that binds specifically to ER, and an antibody that specifically binds to AR; and   (b) predicting that the subject has a relatively elevated risk of developing breast cancer if the frequency of the cells of one or more types is about the same or increased compared to a first control frequency of cells of the one or more types, respectively; or   predicting that the subject has a relatively reduced risk of developing breast cancer if the frequency of the cells of the one or more types is decreased compared to a second control frequency of the cells of the one or more types, respectively.   
     
     
         7 . The method of  claim 6 , wherein the frequency of p27+ breast epithelial cells is determined, and the first control frequency of the p27+ breast epithelial cells is a level that represents 15%, 20%, or 25% of the breast epithelial cells in the sample, and the second control frequency of p27+ breast epithelial cancer cells is a level that represents 15%, 20%, or 25% of the breast epithelial cells in the sample. 
     
     
         8 .- 9 . (canceled) 
     
     
         10 . The method of  claim 6 , wherein the frequency of Ki67+ breast epithelial cells is determined, the first control frequency of the Ki67+ breast epithelial cells is a level that represents 2% of the breast epithelial cells in the sample, and the second control frequency of Ki67+ breast epithelial cells is a level that represents 2% of the breast epithelial cells in the sample. 
     
     
         11 . (canceled) 
     
     
         12 . A method of predicting a subject's risk of developing breast cancer, wherein the method comprises:
 (a) determining the protein or mRNA expression level in a breast tissue sample from a subject of at least one marker selected from the group consisting of p27, Sox17 and Cox2; and   (b) predicting that the subject has a relatively elevated risk of developing breast cancer if the protein or mRNA expression level of the at least one marker is increased compared to a first control level of the at least one marker; or   predicting that the subject has a relatively reduced risk of developing breast cancer if the protein or mRNA expression level of the at least one marker is decreased compared to a second control level of the at least one marker.   
     
     
         13 .- 14 . (canceled) 
     
     
         15 . The method of  claim 12 , wherein step (a) further comprises determining the protein or mRNA expression level of one or more additional markers having an expression level that is modulated in breast epithelial cells of parous women compared to the levels in breast epithelial cells of nulliparous women. 
     
     
         16 . The method of  claim 12 , wherein the sample is enriched for CD44+, CD24− breast epithelial cells, Ki67+ breast epithelial cells, CD44+Ki67+ breast epithelial cells, or CD24+ breast epithelial cells prior to the determining. 
     
     
         17 .- 19 . (canceled) 
     
     
         20 . The method of  claim 1 , wherein the subject has a BRCA1 mutation. 
     
     
         21 . The method of  claim 1 , wherein the subject has a BRCA2 mutation. 
     
     
         22 . The method of  claim 12 , wherein step (a) comprises determining the protein or mRNA expression level of at least two markers selected from the group consisting of p27, Sox17 and Cox2. 
     
     
         23 . The method of  claim 22 , wherein step (a) comprises determining the protein or mRNA expression level of p27, Sox17, and Cox2. 
     
     
         24 . A method of predicting a subject's risk of developing breast cancer, the method comprising:
 determining a parity/nulliparity-associated mRNA expression signature in a sample comprising breast epithelial cells from a subject; and   predicting a subject's risk of developing breast cancer based on the determined parity/nulliparity-associated mRNA expression profile in the sample.   
     
     
         25 . The method of  claim 24 , wherein the sample is enriched for CD44+ cells, CD24+ cells, or CD10+ cells. 
     
     
         26 .- 39 . (canceled) 
     
     
         40 . The method of  claim 1 , wherein the breast cancer is an ER+ breast cancer. 
     
     
         41 . The method of  claim 1 , wherein the breast cancer is an ER− breast cancer.