Methods and kits comprising gene signatures for stratifying breast cancer patients

A method for treating a human subject having a ER+/HER2− breast cancer comprising steps of:

• (a) determining, in a breast tissue or breast cell sample from the subject the expression of 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.