BIOMARKERS FOR BREAST CANCER
The present invention provides protein-based biomarkers and biomarker combinations that are useful in qualifying breast cancer status in a patient. In particular, the biomarkers of this invention are useful to determine metastasis-free survival of breast cancer patients. The biomarkers can be detected by SELDI mass spectrometry in serum samples fractionated by means of anion exchange chromatography. Some of the biomarkers have been identified as: Apolipoprotein A1; Apolipoprotein A2; Haptoglobin alpha 1; Transferrin; Complement C3a; and truncated forms thereof.
1 . A method for determining breast cancer status in a subject comprising:
(a) measuring at least one biomarker in a biological sample from the subject, wherein the at least one biomarker is selected from the group consisting of the biomarkers of Table 1; and
(b) correlating the measurement with breast cancer status.
2 . The method of claim 1 , wherein breast cancer status is relapse of breast cancer versus breast cancer free survival.
3 . The method of any of claims 1 - 2 , wherein the at least one biomarker is measured by capturing the biomarker with a capture reagent on an adsorbent surface of a SELDI probe and detecting the captured biomarker by laser desorption-ionization mass spectrometry.
4 . The method of claim 3 , wherein the capture reagent comprises an antibody.
5 . The method of claim 3 , wherein the capture reagent comprises an IMAC or CM10 sorbent.
6 . The method of any of claims 1 - 2 , wherein the at least one biomarker is measured by immunoassay.
7 . The method of any of claims 1 - 2 , wherein the sample is serum.
8 . The method of any of claims 1 - 2 , wherein the correlating is performed by a software classification algorithm.
9 . The method of any of claims 1 - 2 , further comprising: (c) managing subject treatment based on the status.
10 . The method of claim 9 , further comprising: (d) measuring the at least one biomarker after subject management and correlating the measurement with disease progression.
11 . A method for determining the course of breast cancer comprising:
(a) measuring, at a first time, at least one biomarker in a biological sample from the subject, wherein the at least one biomarker is selected from the group consisting of the biomarkers of Table 1;
(b) measuring, at a second time, the at least one biomarker in a biological sample from the subject; and
(c) comparing the first measurement and the second measurement;
wherein the comparative measurements determine the course of breast cancer.
12 . A method comprising measuring at least one biomarker in a sample from a subject, wherein the at least one biomarker is selected from the group consisting of biomarkers of Table 1.
13 . A composition comprising at least one purified biomolecule selected from the biomarkers of Table 1.
14 . A composition comprising a biospecific capture reagent that specifically binds a biomolecule selected from the biomarkers of Table 1.
15 . The composition of claim 14 , wherein the biospecific capture reagent is an antibody.
16 . The composition of claim 14 , wherein the biospecific capture reagent is bound to a solid support.
17 . A composition comprising a biospecific capture reagent bound to a biomarker of Table 1.
18 . A kit comprising:
(a) a solid support comprising at least one capture reagent attached thereto, wherein the capture reagent binds at least one biomarker selected from the group consisting of the biomarkers of Table 1; and
(b) instructions for using the solid support to detect a biomarker of Table 1.
19 . The kit of claim 18 wherein the solid support comprising a capture reagent is a SELDI probe.
20 . The kit of claim 18 wherein the capture reagent is an antibody.
21 . The kit of claim 18 , additionally comprising: (c) a container containing at least one of the biomarkers of Table 1.
22 . The kit of claim 18 , additionally comprising: (c) a strong cation exchange chromatography sorbent.
23 . A kit comprising:
(a) a solid support comprising at least one capture reagent attached thereto, wherein the capture reagent binds at least one biomarker selected from the group consisting of the biomarkers of Table 1; and
(b) a container containing at least one of the biomarkers.
24 . The kit of claim 23 wherein the solid support comprising a capture reagent is a SELDI probe.
25 . The kit of claim 23 additionally comprising: (c) a strong cation exchange chromatography sorbent.
26 . The kit of claim 23 wherein the capture reagent is an antibody.
27 . A software product comprising:
a. code that accesses data attributed to a sample, the data comprising measurement of at least one biomarker in the sample, the biomarker selected from the group consisting of the biomarkers of Table 1; and
b. code that executes a classification algorithm that classifies the breast cancer status of the sample as a function of the measurement.
28 . The software product of claim 27 , wherein the data comprises measurement of all of the biomarkers of Table 1.
29 . A method comprising detecting at least one biomarker of Table 1 by mass spectrometry or immunoassay.
30 . A method comprising communicating to a subject a diagnosis relating to breast cancer status determined from the correlation of at least one biomarker in a sample from the subject, wherein said at least one biomarker is selected from the group consisting of the biomarkers of Table 1.
31 . The method of claim 30 wherein the diagnosis is communicated to the subject via a computer-generated medium.
32 . A method for identifying a compound that interacts with a biomarker of Table 1, wherein said method comprises:
a) contacting a biomarker of Table 1 with a test compound; and
b) determining whether the test compound interacts with the biomarker.
33 . A method for modulating the concentration of a biomarker of Table 1 in a cell, wherein said method comprises contacting said cell with a compound that modulates the expression of the biomarker.
34 . A method of treating breast cancer in a subject, comprising administering to the subject a therapeutically effective amount of a compound that inhibits expression of an up-regulated biomarker of Table 1.
35 . A method of treating breast cancer in a subject, comprising administering to the subject a therapeutically effective amount of a compound that increases expression of a down-regulated biomarker of Table 1.