US 12,139,766 B2
Methods and kits comprising gene signatures for stratifying breast cancer patients
Pier Paolo Di Fiore, Milan (IT); Salvatore Pece, Milan (IT); Manuela Vecchi, Milan (IT); and Stefano Confalonieri, Milan (IT)
Assigned to Istituto Europeo di Oncologia S.r.l., Milan (IT); Fondazione Istituto Firc di Oncologia Molecolare (IFOM), Milan (IT); and Universita degli Studi di Milano (University of Milan), Milan (IT)
Filed by Istituto Europeo di Oncologia S.r.l., Milan (IT); Fondazione Istituto Firc di Oncologia Molecolare (IFOM), Milan (IT); and Universita degli Studi di Milano (University of Milan), Milan (IT)
Filed on Jul. 29, 2022, as Appl. No. 17/816,210.
Application 17/816,210 is a continuation of application No. 16/308,564, granted, now 11,441,191, previously published as PCT/EP2017/064937, filed on Jun. 19, 2017.
Claims priority of application No. 16175354 (EP), filed on Jun. 20, 2016; and application No. 16188855 (EP), filed on Sep. 14, 2016.
Prior Publication US 2023/0151428 A1, May 18, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. C12Q 1/68 (2018.01); C12P 19/34 (2006.01); C12Q 1/6886 (2018.01); G16B 5/00 (2019.01); G16B 40/00 (2019.01)
CPC C12Q 1/6886 (2013.01) [C12Q 2600/106 (2013.01); C12Q 2600/112 (2013.01); C12Q 2600/118 (2013.01); C12Q 2600/158 (2013.01); C12Q 2600/16 (2013.01); C12Q 2600/166 (2013.01); G16B 5/00 (2019.02); G16B 40/00 (2019.02)] 6 Claims
 
1. A method for treating a human subject having breast cancer comprising steps of:
(a) determining, in a breast tissue or breast cell sample from the subject the expression of a group of genes;
(b) calculating a risk score based upon the expression of the group of genes, wherein a higher risk score indicates an increased risk of breast cancer recurrence in the subject,
wherein the risk score is calculated according to the following formula:
Risk score=Σi(βi*Cqnormalized),
wherein Cqnormalized is calculated according to the following formula:
Cqnormalized=AVG Cq−SF,
wherein SF is the difference between the AVG Cq value of at least one reference gene for each subject and a constant reference value K, wherein K=25.012586069, which represents the mean of the AVG Cq of the at least one reference gene calculated across a plurality of training samples;
(c) stratifying the subject into a high or low risk group; and
(d) administering a breast cancer treatment to the subject, wherein a subject stratified in a high risk group is provided a cancer treatment that is more aggressive than the cancer treatment provided to a subject stratified in a low risk group;
wherein said group of genes consists of:
(i) EIF4EBP1, MRPS23, and TOP2A;
(ii) APOBEC3B, CENPW, EIF4EBP1, EXOSC4, LY6E, MMP1, MRPS23, NDUFB10, and TOP2A;
(iii) ALYREF, APOBEC3B, CDK1, CENPW, EIF4EBP1, EXOSC4, H2AFJ, LY6E, MIEN1, MMP1, MRPS23, NDUFB10, NOL3, RACGAP1, SFN, and TOP2A; or
(iv) H2AFZ, CDK1, EXOSC4, PHLDA2, APOBEC3B, EIF4EBP1, SFN, PHB, EPB41L5, RACGAP1, MRPS23, TOP2A, H2AFJ, NOL3, MIEN1, CENPW, LY6E, ALYREF, MMP1, and NDUFB10.