Prognostic and predictive breast cancer signature
Embodiments of the invention are directed to methods of determining the prognosis of a breast cancer patient by evaluating a specified set of genes. Specifically, methods may comprise calculating a prognosis score based on a particular algorithm. Also disclosed are compositions, kits and methods for treating cancer in a subject in need thereof are disclosed involving one or more upstream activators and/or downstream effectors of TET1.
1. A method of treating a patient determined to have a breast cancer, comprising administering a treatment comprising anthracyclines, taxanes, beta-blockers, ixabepilone, bevacizumab, eribulin, or platinum-based therapy alone or combined with surgery to a patient identified as being at a low risk for metastasis by identifying a breast cancer sample from the patient as having, relative to a control or reference sample, decreased expression or activity of at least four biomarkers of the following seven biomarkers: RKIP, MMP1, OPN, HMGA2, CXCR4, let-7, and BACH1, wherein the at least four biomarkers comprise BACH1, and wherein identifying the breast cancer sample as having decreased expression or activity of BACH1 comprises identifying the breast cancer sample as having decreased expression of PRDM1.
2. The method of claim 1 , wherein the platinum-based therapy is administered to the patient.
3. The method of claim 1 , wherein the breast cancer is a basal-like breast cancer or triple negative breast cancer.
4. The method of claim 1 , wherein the control or reference sample is a breast cancer sample from a patient identified as being at a high risk for metastasis.
5. The method of claim 1 , wherein the at least four biomarkers comprise RKIP, MMP1, OPN, HMGA2, CXCR4, and BACH1.
6. The method of claim 1 , wherein identifying the breast cancer sample as having decreased expression or activity of BACH1 further comprises identifying the breast cancer sample as having decreased expression of at least two of BMPER, DYM, FBXO42, FRMPD4, HERC3, HS3ST3B1, IL1RAP, IL7, MAGEC1, MYCT1, PDE1C, and RCAN3.
7. The method of claim 1 , wherein identifying the breast cancer sample as having decreased expression or activity of BACH1 comprises identifying the breast cancer sample as having decreased expression of BMPER, DYM, FBXO42, FRMPD4, HERC3, HS3ST3B1, IL1RAP, IL7, MAGEC1, MYCT1, PDE1C, PRDM1, and RCAN3.
8. The method of claim 1 , wherein the at least four biomarkers comprise RKIP, MMP1, OPN, HMGA2, CXCR4, let-7, and BACH1.
9. The method of claim 1 , wherein the at least four biomarkers further comprise let-7, and wherein identifying the breast cancer sample as having decreased expression or activity of let-7 comprises identifying the breast cancer sample as having increased expression of at least two of ARID3B, CCNJ, GOLT1B, HIC2, IGF2BP3, IL13, MAP4K4, NF2, PAPPA, SLC6A1, TGFBR1, and ZC3H3.
10. The method of claim 1 , wherein the at least four biomarkers further comprise let-7, and wherein identifying the breast cancer sample as having decreased expression or activity of let-7 comprises identifying the breast cancer sample as having increased expression of ARID3B, CCNJ, GOLT1B, HIC2, IGF2BP3, IL13, MAP4K4, NF2, PAPPA, SLC6A1, TGFBR1, and ZC3H3.
11. The method of claim 1 , wherein the at least four biomarkers further comprise let-7, and wherein:
(a) identifying the breast cancer sample as having decreased expression or activity of BACH1 further comprises identifying the breast cancer sample as having decreased expression of RKIP, MMP1, OPN, HMGA2, CXCR4, BMPER, DYM, FBXO42, FRMPD4, HERC3, HS3ST3B1, IL1RAP, IL7, MAGEC1, MYCT1, PDE1C, and RCAN3; and
(b) identifying the breast cancer sample as having decreased expression or activity of let-7 comprises identifying the breast cancer sample as having increased expression of ARID3B, CCNJ, GOLT1B, HIC2, IGF2BP3, IL13, MAP4K4, NF2, PAPPA, SLC6A1, TGFBR1, and ZC3H3.