Methods of treating breast cancer

A method of treating cancer in a metastatic estrogen receptor positive breast cancer subject, the method comprising:

• (a) measuring an expression level of a transcriptome set of RNA transcripts in a plurality of cells obtained from a tumor from a metastatic estrogen receptor positive breast cancer subject, wherein the transcriptome set of RNA transcripts comprises RNA transcripts expressed from:
• (i) an endocrine signaling negative gene set, wherein said endocrine signaling negative gene set comprises at least 5 genes selected from ASF1B, CDCA8, HJURP, NCAPG, STIL, ASPM, CENPA, hNp95, NUSAP1, TACC3, AURKA, CENPE, KIF14, OIP5, AURKB, CENPF, KIF15, PKMYT1, TOP2A, BIRC5, CEP55, KIF20A, PLK1, TPX2, BUB1, CKAP2L, KIF23, PLK4, TRIP13, CCNA2, DLGAP5, KIF2C, POLQ, TROAP, CCNB2, E2F2, KIF4A, PRC1, TTK, CDC20, CDC25C, ESPL1, KIFC1, PTTG1, UBE2C, CDC25, EXO1, MCM10, PTTG3, TIMELESS, UBE2S, CDC45, FAM64A, MCM2, RACGAP1, ZWINT, CDCA3, FOXM1, MELK, RECQL4, CDCA5, GSK3B, MKI67, or SPC25;
• (ii) an endocrine signaling positive gene set, wherein said endocrine signaling positive gene set comprises at least 5 genes selected from GREB1, CA12, SLC9A3R1, MYB, ANXA9, IGFBP4, SYBU, NPY1R, PDZK1, NRIP1, MLPH, HSPB8, EGR3, KRT19, LRIG1, KDM4B, PGR, RHOBTB3, TPD52L1, ELOVL2, RET, TPBG, TFF1, MAPT, SCNN1A, ABAT, FLNB, XBP1, CELSR2, RAB31, MYBL1, MREG, FAM102A, MSMB, STC2, RETREG1, SIAH2, SLC27A2, FKBP4, CXCL12, TMPRSS3, RARA, IL17RB, CBFA2T3, TFF3, UGCG, CCND1, SLC22A5, WFS1, PTGES, WWC1, CCN5, MYC, ITPK1, TMEM164, ARL3, MED13L, SEMA3B, KRT18, SLC16A1, TJP3, SLC26A2, FCMR, SULT2B1, SNX24, TFAP2C, TTC39A, GJA1, PRSS23, OLFM1, RAPGEFL1, ASB13, TIPARP, ABCA3, PLAAT3, SLC7A5, MPPED2, TIAM1, CLDN7, MYOF, RBBP8, OLFML3, GFRA1, FARP1, SVIL, TGM2, DEPTOR, CYP26B1, PAPSS2, SLC1A1, DLC1, JAK2, AFF1, KLK10, P2RY2, BLVRB, CISH, GLA, ADD3, PDLIM3, MINDY1, FOS, KRT8, SLC37A1, B4GALT1, CALCR, ESRP2, IGF1R, NBL1, SFN, OPN3, TUBB2B, TBC1D30, SEC14L2, ENDOD1, HR, SCARB1, NCOR2, RHOD, INPP5F, PPIF, DHRS3, FDFT1, GAB2, UNC119, KLF10, HES1, FKBP5, SLC2A1, AMFR, NADSYN1, INHBB, BHLHE40, CALB2, FASN, CHPT1, MYBBP1A, ELOVL5, DYNLT3, ABLIM1, SOX3, SLC24A3, RAB17, MAST4, KCNK5, ELF1, RPS6KA2, ISG20L2, ZNF185, SLC19A2, SLC1A4, FHL2, BCL2, PMAIP1, AREG, OVOL2, TSKU, ADCY9, RASGRP1, MUC1, KAZN, FRK, DHRS2, AQP3, KCNK15, TGIF2, FOXC1, ELF3, REEP1, PEX11A, PODXL, KLF4, BAG1, CELSR1, ABHD2, AR, SLC39A6, SYT12, CD44, MED24, BCL11B, CANT1, KRT13, KRT15, TOB1, IL6ST, SYNGR1, SH3BP5, ALDH3B1, THSD4, CLIC3, NXT1, NAV2, RRP12, ADCY1, DHCR7, MICB, AKAP1, SLC7A2, or LAD1;
• and
• (iii) a remainder gene set, wherein said remainder gene set consists of all genes expressing said transcriptome set of RNA transcripts except said endocrine signaling positive gene set and said endocrine signaling negative gene set;
• (b) determining a first aggregate rank of the expression level of RNA transcripts from the endocrine signaling negative gene set relative to the expression level of RNA transcripts from said remainder gene set and calculating an empirical gene set enrichment score (GESemp);
• (c) determining a second aggregate rank of the expression level of RNA transcripts from an endocrine signaling positive gene set relative to the expression level of RNA transcripts from said remainder gene set and calculating an estrogen response gene set enrichment score (GESer);
• (d) calculating a risk score according to according to the function:
• exp
• ⁢
• (
• 1.54
• ×
• GES
• emp
• +
• -
• 2.72
• ×
• GES
• er
• )
• when said risk score is greater than or equal to 2, administering chemotherapy to said metastatic estrogen receptor positive breast cancer subject and not administering anticancer endocrine therapy to said metastatic estrogen receptor positive breast cancer subject, and
• when said risk score is less than 2, administering anticancer endocrine therapy to said metastatic estrogen receptor positive breast cancer subject and not administering chemotherapy to said metastatic estrogen receptor positive breast cancer subject.