Supplemental Data Table 1 Characteristics of the MHH BC cohort number percent cases 183 100 histology IDBC 128 70 ILBC 49 27 others 6 3 pt status pt1 98 54 pt2 56 31 pt3 14 8 pt4 14 8 ptx 1 1 pn status pn0 95 52 pn1+ 65 36 pnx 23 13 histological grade G1 15 8 G2 106 58 G3 62 34 ER positive 36 20 negative 147 80 PR positive 78 43 negative 105 57 AR positive 96 52 negative 53 29 n.a. 34 19 HER2 0, 1+ 172 94 2+ (FISH-neg.) 3 2 3+ 8 4 p53 positive 159 87 negative 24 13 BCL2 positive 84 46 negative 99 54 CK5/14 positive 168 92 negative 15 8 E-cadherin positive 52 28 negative 131 72 EGFR positive 181 99 negative 2 1 Ki67 <5%, 5% 42 23 10%, 15% 61 33 20%, 25% 34 19 30%, 35% 14 8 40%, >40% 32 17 AP-2 negative 71 39 positive 112 61
Supplemental Data Table 2 Characteristics of the WSG PlanB BC cohort (limited to ER+/HER2- cases) number percent cases 2232 100 histology IDBC 1923 86 ILBC 309 14 pt status pt1 1078 48 pt2 813 36 pt3 73 3 pt4 13 1 ptx 255 11 pn status pn0 1317 59 pn1 785 35 pn2 99 4 pn3 31 1 histological grade G1 100 4 G2 1402 63 G3 730 33 PR positive 399 18 negative 1809 81 n.a. 24 1 Ki67 <5%, 5% 479 21 10%, 15% 872 39 20%, 25% 560 25 30%, 35% 141 6 40%, >40% 77 3 n.a. 103 5 ODX RS 0-11 396 18 12-18 770 34 19-25 567 26 26-30 189 8 >30 257 11 n.a. 53 2 AP-2 negative 1045 47 positive 1187 53
Supplemental Data Table 3 Characteristics of mouse mammary specimens of genetically engineered models strain promoter transgene conditional additional information histology specimens negative weak/moderate strong element knock out / in (IRS 0-2) (IRS 3-9) (IRS12) FVB/N juvenile normal 4 2 2 0 NMRIxC57BL/6 adult normal lactating 1 1 0 0 Balb/c adult 30 day post weaning normal, involution 2 2 0 0 Balb/c adult 50 day post weaning normal, involution 3 3 0 0 Balb/c (T1) WAP sv40-t-ag Wsv40-T-ag, involution, 30 pw ductal carcinoma in situ 2 2 0 0 Balb/c (T1) WAP sv40-t-ag Wsv40 induced murine mammary carcinoma T1 ductal carcinoma 5 5 0 0 Balb/c WAP Cre Pik3CA H1047R Wcre; Pik3CA H1047R adenoasquamous carcinoma 5 5 0 0 Balb/c WAP Cre Pik3CA H1047R Wcre; Pik3CA H1047R adenocarcinoma 2 2 0 0 Balb/c MMTV Cre Pik3CA H1047R MMTVcre; Pik3CA H1047R adenomyoepithelioma 5 5 0 0 FVB/N WAP Cre Trp53 Wcre-het; Trp53 F/F ; Cdh1 F/+ adenocarcinoma 13 13 0 0 or Wcre-het; Trp53 F/F FVB/N WAP Cre Trp53 Wcre-het; Trp53 F/F ; Cdh1 F/+ solid carcinoma 19 19 0 0 or Wcre-het; Trp53 F/F FVB/N WAP Cre Trp53 and Cdh1 Wcre-het; Trp53 F/F ; Cdh1 F/F, solid carcinoma 11 11 0 0 or Wcre-het; Trp53 F/+ ; Cdh1 F/F FVB/N WAP Cre Trp53 and Cdh1 Wcre-het; Trp53 F/F ; Cdh1 F/F lobular carcinoma 19 19 0 0 or Wcre-het; Trp53 F/+ ; Cdh1 F/F FVB/N WAP Cre Trp53 and Cdh1 Wcre-het; Trp53 F/F ; Cdh1 F/F metastasis 18 18 0 0 or Wcre-het; Trp53 F/+ ; Cdh1 F/F FVB/N WAP Cre Cdh1 and Pten WCre;Cdh1 F/F ; Pten F/F lobular carcinoma 5 5 0 0 total 114 112 2 0
Supplemental Data Table 4 Antibodies used for immunohistochemical analysis in MHH cohort antigen antibody species source dilution antigenic retrieval detection system scoring cutoff ER clone SP1 rabbit Ventana undiluted, readyto-use PR clone 1E2 rabbit Ventana undiluted, readyto-use AR AR441 mouse Dako 1:40 ErbB2 clone NCL-c-erbB2p mouse Novocastra 1:400 citric acid, ph 6.0, p53 Do-7 mouse Novocastra 1:100 citric acid, ph 6.0, BCL2 clone 124 mouse Dako 1:100 CK5/14 clones XM26 & LL002 mouse Zytomed 1:200 citric acid, ph 6.0, E-cadherin clone 4A2C7 mouse Invitrogen 1:50 citric acid, ph 6.0, EGFR clone 2.1E1 mouse Zytomed 1:600 Fast Enzyme Solution Ki67 Clone30-9 rabbit Ventana undiluted, readyto-use 0, 1+, 2+, 3+ 2+ very strong nuclear staining > 90 % of tumor cells semiquantitative, 0-100 10, 25
Supplemental Data Table 5 Antibodies used for immunohistochemical analysis in Plan B cohort antigen antibody species source dilution antigenic retrieval detection system scoring cutoff E-cadherin 4A2C7 mouse Invitrogen 1:50 citric acid, ph 6.0, ER clone SP1 rabbit Neomarkers/MEDAC 1:100 citric acid, ph 6.0, PR PgR636 mouse Dako 1:100 citric acid, ph 6.0, Ki67 Clone 30-9 rabbit Ventana undiluted, ready-to-use ultraview DAB Kit Semiquantitative, 0-100 10, 25
Supplemental Data Table 6 AP-2 expression in human embryonic tissues mouse embryo human embryo selected anatomical day 11-16 p.c. 8 weeks gest. age structures (Moser et al. 1997) (this study) dorsal roof of the midbrain + + hindbrain + + facial mesenchyme + + tounge, upper surface + + tongue, lower surface - - epidermis + + liver - - sceletal muscle - - mesometanephric anlage + +