US 9,803,245 B2 · Signature for predicting clinical outcome in human HER2+ breast cancer

Abstract

A method of predicting outcome in a subject with for example Her2+ (ERα−) breast cancer comprising: (a) determining a HTICs expression signature comprising determining an expression level of 2 or more HTICS biomarkers selected from Aurkb, Ccna2, Scrn1, Npy, Atp7b, Chaf1b, Ccnb1, Cldn8, Nrp1, Ccr2, C1qb, Cd74, Vcam1, Cd180, Itgb2, Cd72, St8sia4, Kif11, Plk1, Chek1, Mphosph6, Cora1a, Ccl5, Cd3e, Hcls1, Vav1, Plek, Arhgdib, Il2rg, Sash3, Lck, Il2rb, Cybb, Cd79b, Sell, Ccnd2, Tnfrsf1b, Rftn1, Rac2 and Ly86; and (b) calculating a signature score, the signature score comprising a sum of HTICs biomarker expression parameters; wherein a signature score greater than a selected cut-off or control signature score is indicative of a poor outcome (HTICS+) and a signature score less than a selected cut-off is indicative of a good outcome (HTICS−). The methods can be used to prognose outcome and/or select suitable treatment. Arrays and kits for use with the methods are also provided.

Claims9

Dependent claims

A method of treating a subject afflicted with HER2+ ERα negative breast cancer, the method comprising:

a. obtaining a subject test sample;
b. for each of a plurality of HTICs biomarkers, using a biomarker specific probe to determine a RNA expression level for each of the plurality of HTICs biomarkers in the test sample, the HTICs biomarkers consisting of Group (A) Aurkb, Ccna2, Scrn1, Npy, Atp7b, Chaf1b, Ccnb1 and Cldn8, and Group (B) Nrp1, Ccr2, C1qb, Cd74, Vcam1, Cd180, Itgb2, Cd72 and St8sia4;
c. calculating a signature score match (SSM) according to the formula
Σ(InXn/|Xn|)/Σ(|In|);
where I is the gene index for each HTICs biomarker (n) wherein the gene index of 1 is used for HTICs biomarkers which are up-regulated genes in TICs and the gene index −1 for down-regulated genes in TICs;
X is the log 2 transformed and median-centered and/or normalized RNA expression level for each HTICs biomarker (n);
and
d. administering adjuvant anti-HER2 treatment to the subject when the subject is identified as having a SSM of greater than and/or equal to 0 and administering treatment excluding adjuvant anti-HER2 treatment when the SSM score is less than 0.

5 more elements

Dependencies are inferred from the claim text.

Signature for predicting clinical outcome in human HER2+ breast cancer

Life of this patent

Signature for predicting clinical outcome in human HER2+ breast cancer

Life of this patent

Abstract

Claims9