Supplemental Figure 1

FAC (n=143) TFAC (n=279) TA (n=488) Median Age 48 (26-78) 51 (26-79) 49 (24-75) ER-positive 72 (50.35%) 162 (58.06%) 285 (59.13%) ER-negative 71 (49.65%) 117 (41.94%) 197 (40.87%) Her2-positive 49 (17.56%) 5 (1.02%) Her2-negative 143 (100%) 230 (82.44%) 472 (96.72%) Her2-unavailable 11 (2.25%)

Supplemental Figure 1: Demographic data from the datasets that were employed in this study Aebp2 ae binding pro Anapc11 apc11 anaphas Supplemental Figure 2 Anapc5 prom Angptl2 angiopoietin-li Anln anillin, bi Anp32b acidic (leucine- Arhgap21 rho gtpase act Asf1b asf1 anti-silenc Atm ataxia telangie Birc5 baculoviral iap Brca1 breast cancer Brca2 breast cancer Brrn1 barren homolo Bub1 bub1 budding Casppp8ap2 casp8 associat Cbx2 chromobox ho Cbx5 chromobox ho Ccna2 cyclin a2 Ccnb1 cyclin b1 Ccnb2 cyclin b2 Ccnf cyclin f Cd34 cd34 antigen Cdc20 cdc20 cell divis Cdc25c cy Cdc45l cdc45 cell divis Cdc6 cdc6 cell divisi Cdca3 cell division cy Cdca5 cell division cy Cdca7 cell division cy Cdca8 cell division cy Cdk2 cyclin-depende Cdkn1c cyclin-depende Cdkn3 cyclin-depende Cenpa centromere pro Chaf1b chromatin asse Chek1 chk1 checkpoin Ckap2 a Cks2 cdc28 Dck deoxycytidine Ddit4 dna-damage-in Dek dek oncogene Dlg7 discs, large ho Dnajc9 dnaj (hsp40) h Dnmt1 dna (cytosine- Dok1 docking protei Dtymk deoxythymidyl E2f1 e2f transcriptio Ect2 epithelial cell t Egr1 early growth re Ei24 etoposide indu Eif4a2 eukaryotic tran Ercc5 excision repair Etv4 ets variant gen Ezh2 enhancer of ze Fbln1 fibulin 1 Fen1 flap structure- Fez1 fasciculation a Foxm1 forkhead box m Gmnn geminin, dna r Gtse1 g- 2 and s -phas H2afz h2a histone fa Hat1 histone acetylt Helb helicase (dna) Hip1r huntingtin inte Hmga2 high mobility g Hmgb2 high-mobility g Hmgb3 high-mobility g Hmgn1 high-mobility g Hmgn2 high-mobility g Hnrpc heterogeneous Hnrpd heterogeneous Hnrpr heterogeneous Hnrpu heterogeneous Incenp inner centrome Kif11 kinesin family Kif1c kinesin family Kif20a kinesin family Kif22 kinesin family Kif23 kinesin family Kif2c kinesin family Klf4 kruppel-like fa Kpna2 karyopherin al Lbr lamin b recept Lig1 ligase i, dna, a Mad2l1 mad2 mitotic a Mcm2 mcm2 minichr Mcm3 mcm3 minichr Mcm4 mcm4 minichr Mcm5 mcm5 minichr Mcm7 mcm7 minichr Mdm2 mdm2, transfo Mki67 antigen identif Mre11a mre11 meiotic Msh2 muts homolog Mtcp1 mature t-cell p Nap1l1 nucleosome as Nasp nuclear autoan Nek2 nima (never in Nusap1 nucleolar and s Orc6l origin recognit Pcna proliferating ce Pdcd6ip programmed c Pdgfra platelet-derive Perp perp, tp53 apo Phc1 polyhomeotic- Phf13 phd finger prot Plk1 polo-like kinas Plk4 polo-like kinas Pltp phospholipid tr Pml promyelocytic Pold1 polymerase (d Prc1 protein regulat Prdx4 peroxiredoxin Prim1 primase, polyp Psip1 pc4 and sfrs1 Racgap1 rac gtpase acti Rad21 rad21 homolog Rad51 rad51 homolog Rad51ap1 rad51 associat Rbbp4 retinoblastoma Rbl1 retinoblastoma Rev3l rev3-like, cata Rfc2 replication fact Rfc5 replication fact Rgnef rho-guanine nu Rpa1 replication pro R1Rrm1 ribonuc leo tide Rrm2 ribonucleotide Siva cd27-binding ( Slbp stem-loop (his Slk ste20-like kina Smc2l1 smc2 structura Smc4l1 smc4 structura Stmn1 1/onc Tacc3 transforming, Tardbp tar dna binding Tcf19 transcription fa Tfdp1 transcription fa Tk1 thymidine kina Tmpo thymopoietin Top2a topoisomerase Topbp1 topoisomerase Trip13 thyroid hormo Ttk ttk protein kina Tubgcp3 , gamm Tyms thymidylate sy Uhrf1 ubiquitin-like,

Supplemental Figure 2: comprising the RB- loss signature used in this study Rb p16 ------Supplemental Figure 3 taxane-anthracycline response in GSE25066, all patients taxane-anthracycline response in GS TP = 76 TP = 75 FP = 158 FP = 159 TN = 231 TN = 230 FN = 23 FN = 24 PPV = 0.32479 PPV = 0.32051 NPV = 0.90945 NPV = 0.90551 sens = 0.76768 sens = 0.75758 spec = 0.59383 spec = 0.59126 ------taxane-anthracycline response in GSE25066, all patients threshold from 2010 paper: TP = 71 FP = 138 TN = 163 FN = 10 PPV = 0.33971 NPV = 0.9422 sens = 0.87654 spec = 0.54153 ------taxane-anthracycline response in GSE25066, ER-positive ptaxane-anthracycline response in GS TP = 23 TP = 18 FP = 75 FP = 77 TN = 180 TN = 178 FN = 7 FN = 12 PPV = 0.23469 PPV = 0.18947 NPV = 0.96257 NPV = 0.93684 sens = 0.76667 sens = 0.6 spec = 0.70588 spec = 0.69804 ------taxane-anthracycline response in GSE25066, ER-positive patients threshold from 2010 paper: TP = 21 FP = 62 TN = 136 FN = 3 PPV = 0 . 25301 NPV = 0.97842 sens = 0.875 spec = 0.68687 ------taxane-anthracycline response in GSE25066, ER-negative taxane-anthracycline response in GS TP = 52 TP = 56 FP = 81 FP = 81 TN = 48 TN = 48 FN = 16 FN = 12 PPV = 0.39098 PPV = 0.40876 NPV = 0.75 NPV = 0.8 sens = 0.76471 sens = 0.82353 spec = 0.37209 spec = 0.37209 ------taxane-anthracycline response in GSE25066, ER-negative patients threshold from 2010 paper: TP = 50 FP = 74 TN = 27 FN = 7 PPV = 0.40323 NPV = 0.79412 sens = 0.87719 spec = 0.26733 ------response in all FAC, all patients response in all FAC, all patients TP = 32 TP = 34 FP = 35 FP = 40 TN = 64 TN = 59 FN = 12 FN = 10 PPV = 0.47761 PPV = 0.45946 NPV = 0.84211 NPV = 0.85507 sens = 0.72727 sens = 0.77273 spec = 0.64646 spec = 0.59596 ------response in all FAC, all patients threshold from 2010 paper: TP = 34 FP = 36 TN = 29 FN = 2 PPV = 0.48571 NPV = 0.93548 sens = 0.94444 spec = 0.44615 ------response in all FAC, ER- positive patients response in all FAC, ER- positive pat TP = 10 TP = 8 FP = 14 FP = 17 TN = 42 TN = 39 FN = 6 FN = 8 PPV = 0.41667 PPV = 0.32 NPV = 0.875 NPV = 0.82979 sens = 0.625 sens = 0.5 spec = 0.75 spec = 0.69643 ------response in all FAC, ER-positive patients threshold from 2010 paper: TP = 11 FP = 14 TN = 19 FN = 1 PPV = 0.44 NPV = 0.95 sens = 0.91667 spec = 0.57576 ------response in all FAC, ER-negative patients response in all FAC, ER-negative pa TP = 22 TP = 26 FP = 21 FP = 23 TN = 22 TN = 20 FN = 6 FN = 2 PPV = 0.51163 PPV = 0.53061 NPV = 0.78571 NPV = 0.90909 sens = 0.78571 sens = 0.92857 spec = 0.51163 spec = 0.46512 ------response in all FAC, ER-negative patients threshold from 2010 paper: TP = 23 FP = 22 TN = 10 FN = 1 PPV = 0.51111 NPV = 0.90909 sens = 0.95833 spec = 0.3125

Rb p16 ------response in all TFAC, all patients response in all TFAC, all patients TP = 46 TP = 37 FP = 92 FP = 69 TN = 124 TN = 147 FN = 17 FN = 26 PPV = 0.33333 PPV = 0.34906 NPV = 0.87943 NPV = 0.84971 sens = 0.73016 sens = 0.5873 spec = 0.57407 spec = 0.68056 ------response in all TFAC, all patients threshold from 2010 paper: TP = 43 FP = 83 TN = 90 FN = 8 PPV = 0.34127 NPV = 0.91837 sens = 0.84314 spec = 0.52023 ------response in all TFAC, ER-positive patients response in all TFAC, ER-positive p TP = 9 TP = 8 FP = 55 FP = 35 TN = 94 TN = 114

Supplemental Figure 3: The sensitivity, specificity, negative and positive predictive value of the RB-signature, p16ink4a, and RB protein is provided for each cohort analyzed Supplemental Figure 4

ER-neg ER-pos RB-negative 15 (58%) 11 (42%) RB-positive 14 (20%) 57 (80%)

HER2-neg HER2-pos RB- negative 19 (83%) 4 (17%) RB-positive 41 (72%) 16 (28%)

Grade (1,2) Grade (3) RB-negative 10 (40%) 15 (60%) RB-positive 43 (63%) 25 (37%)

RB-negative breast cancer is associated with ER-negative disease (p<0.05) Advanced nuclear grade (p<0.05)

pCR as a function of RB-status and ER-status RB-negative: pCR 42.3% ER-positive: 4 (36.4%) ER-negative: 7 (46.7%)

RB-positive: pCR 12.8% ER-positive: 5 (8.8%) ER-negative: 3 (21.4%)

Supplemental Figure 4: The association of RB immunohistochemical status with ER, Her2 and Grade is provided, as is the association of RB and ER status with pathological complete response in the TJU cohort. Supplemental Figure 5

Supplemental Figure 5: Analyses of RB-loss signature in Her2 positive breast cancer cases treated with TFAC.