Method, Array and Use Thereof

Abstract

The present invention provides a method for the prognosis of breast cancer in a subject comprising the steps of: (a) providing a first proteome sample from the subject; (b) measuring in the first proteome sample the amount of one or more biomarkers selected from the group of biomarkers listed in Table 1; (c) providing an additional (e.g. a second) proteome sample from the subject; (d) measuring in the additional proteome sample the amount of the one or more biomarkers selected from the group of biomarkers listed in Table 1 measured in step (b); and (e) determining the difference between the amount of the one or more biomarkers in the first and additional proteome samples; wherein the first proteome sample and additional proteome sample are representative of the proteome composition of the subject on different days, and wherein the difference between the amount of the one or more biomarkers in the first and additional (e.g. second) proteome samples is indicative of the risk of recurrence and/or metastasis of the breast cancer in the subject. In further embodiments, step (b) comprises measuring the amount of each the biomarkers listed in Table 1(A) or all of the biomarkers listed in Table 1. The present invention additionally provides an array for performing the method of the invention, the use in vitro of a biomarker selected from the group of biomarkers in Table 1 as a prognostic marker for determining risk of recurrence and/or metastasis of breast cancer in a subject, and a kit for performing the method of the invention comprising one or more binding agents capable of binding to a biomarker listed in Table 1.

1 . A method for the prognosis of breast cancer in a subject comprising the steps of:
 (a) providing a first proteome sample from the subject;   (b) measuring in the first proteome sample the amount of one or more biomarkers selected from the group of biomarkers in Table 1;   (c) providing an additional proteome sample from the subject;   (d) measuring in the additional proteome sample the amount of the one or more biomarkers measured in step (b);   (e) determining the difference between the amount of the one or more biomarkers in the first proteome sample and the additional proteome sample;   wherein the first proteome sample and additional proteome sample are representative of the proteome composition of the subject on different days,   and wherein the difference between the amount of the one or more biomarkers in the first and additional proteome samples is indicative of the risk of recurrence and/or metastasis of breast cancer in the subject.   
     
     
         2 . The method according to  claim 1  wherein steps (c) and (d) are repeated in order to provide one or more further proteome samples from the subject and to measure therein the amount of the one or more biomarkers measured in step (b), wherein the one or more further proteome samples are representative of the proteome composition of the subject on different days from the first and second proteome samples. 
     
     
         3 - 6 . (canceled) 
     
     
         7 . The method according to  claim 1  wherein step (b) comprises measuring the amount of 1 or more biomarkers from the biomarkers listed in Table 1(A), for example at least 2 of the biomarkers listed in Table 1(A). 
     
     
         8 . The method according to  claim 1  wherein step (b) comprises measuring the amount of 1 or more biomarkers from the biomarkers listed in Table 1(B), for example at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18 or 19 of the biomarkers listed in Table 1(B). 
     
     
         9 . (canceled) 
     
     
         10 . The method according to  claim 1  wherein step (b) comprises measuring the amount of 1 or more biomarkers from the biomarkers listed in Table 1(C), for example at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or all 15 of the biomarkers listed in Table 1(C). 
     
     
         11 . The method according to  claim 1  wherein step (b) comprises measuring the amount of all of the biomarkers listed in Table 1. 
     
     
         12 . The method according to  claim 1  wherein step (b) and/or step (d) is performed using one or more binding agents capable of binding to a biomarker listed in Table 1. 
     
     
         13 . The method according to  claim 1  wherein the one or more binding agents each comprise or consist of an antibody or antigen-binding fragment thereof. 
     
     
         14 - 19 . (canceled) 
     
     
         20 . The method according to  claim 1  wherein step (b) and/or step (d) are performed using an array. 
     
     
         21 - 23 . (canceled) 
     
     
         24 . The method according to  claim 1  wherein the samples provided in step (a) and/or step (c) are treated prior to step (b) and/or step (d), respectively, such that any biomarkers present in the samples are labelled with a detectable moiety. 
     
     
         25 - 32 . (canceled) 
     
     
         33 . The method according to  claim 1  wherein the first proteome sample and additional proteome sample are representative of the proteome composition of the subject on different days at least 7 days apart, for example, at least 14 days apart, at least 21 days apart, at least 28 days apart or at least 35 days apart. 
     
     
         34 . The method according to  claim 1  wherein the first proteome sample, provided in step (a), is representative of the proteome composition of the subject at a time point within about 4 weeks before or after resection of a breast cancer tumour in the subject. 
     
     
         35 . The method according to  claim 1  wherein the first proteome sample is representative of the proteome composition of the subject at a time point about 4 weeks before resection of a breast cancer tumour in the subject, for example, about 3 weeks, 2 weeks, 1 week, 6 days, 5 days, 4 days, 3 days, 2 days, 1 day or 0 days before tumour resection. 
     
     
         36 . (canceled) 
     
     
         37 . (canceled) 
     
     
         38 . The method according to  claim 1  wherein the additional proteome sample is representative of the proteome composition of the subject at a time point within 3 to 6 months after tumour resection. 
     
     
         39 . The method according to  claim 1  wherein step (c) and step (d) are repeated such that further proteome samples are provided and biomarker levels therein measured, wherein the further proteome samples are representative of the proteome composition of the subject at a time point every 6 to 18 months after tumour resection, up to at least 24 months. 
     
     
         40 - 47 . (canceled) 
     
     
         48 . The method according to  claim 1  wherein the predicative accuracy of the method, as determined by an ROC AUC value, is at least 0.70, for example at least 0.75, 0.80 or at least 0.85. 
     
     
         49 - 53 . (canceled) 
     
     
         54 . An array for performing the method according to  claim 1  comprising one or more binding agents capable of binding to a biomarker listed in Table 1. 
     
     
         55 - 57 . (canceled) 
     
     
         58 . The array according to  claim 54  comprising one or more binding agents capable of binding to each of the biomarkers listed in Table 1. 
     
     
         59 - 66 . (canceled) 
     
     
         67 . A method for determining risk of recurrence and/or metastasis of breast cancer in a subject, said method comprising measuring a biomarker selected from the group of biomarkers in Table 1. 
     
     
         68 - 70 . (canceled) 
     
     
         71 . A kit for performing a method according to  claim 1  comprising one or more binding agents capable of binding to a biomarker listed in Table 1. 
     
     
         72 - 88 . (canceled)