Claims for Patent: 9,803,245

Summary for Patent: 9,803,245

Title:	Signature for predicting clinical outcome in human HER2+ breast cancer
Abstract:	A method of predicting outcome in a subject with for example Her2+ (ER.alpha.-) 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.
Inventor(s):	Zacksenhaus; Eldad (Toronto, CA), Liu; Jeff (Toronto, CA)
Assignee:	University Health Network (Toronto, CA)
Application Number:	13/829,234
Patent Claims:	1. A method of treating a subject afflicted with HER2+ ER.alpha. 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 .SIGMA.(I.sub.nX.sub.n/|X.sub.n|)/.SIGMA.(|I.sub.n|); 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. 2. The method of claim 1, wherein a SSM of greater than and/or equal to 0 is an indication of having an increased likelihood of a poor response to treatment without adjuvant anti-HER2 treatment and a SSM of less than 0 is an indication of having an increased likelihood of a good response to treatment without adjuvant anti-HER2 treatment. 3. The method of claim 2, wherein the poor response to treatment indicates decrease in likelihood of survival, decrease likelihood of disease free survival and/or decreased likelihood of metastasis free survival. 4. The method of claim 1, wherein the HER2+ ER.alpha. negative breast cancer is node positive. 5. The method of claim 1, wherein the adjuvant anti-HER2 treatment comprises trastuzamab, pertuzumab or lapatinib treatment. 6. The method of claim 1, wherein the HTICs expression signature is determined in a formalin fixed, parafilm embedded (FFPE) test sample. 7. A method of treating a HER2+ ER.alpha. negative breast cancer subject in need thereof comprising: administering chemotherapy and adjuvant anti-HER2 treatment to the subject when the subject is identified as having a signature score match (SSM) greater than and/or equal to 0 and administering chemotherapy without adjuvant anti-HER2 treatment to the subject when the subject is identified as having a SSM less than 0, wherein the SSM is calculated according to the formula .SIGMA.(I.sub.nX.sub.n/|X.sub.n|)/.SIGMA.(|I.sub.n|); where I is the gene index for each HTICs biomarker (n), 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, wherein the gene index of 1 is used for HTICs biomarkers which are up-regulated genes in TICs and the gene index of -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). 8. The method of claim 7, wherein the adjuvant anti-HER2 treatment comprises trastuzamab, pertuzumab or lapatinib treatment. 9. The method of claim 7, wherein the HER2+ ER.alpha. negative breast cancer is node-positive.

Details for Patent 9,803,245

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	PERJETA	pertuzumab	Injection	125409	06/08/2012		2032-03-14