Supplemental Data Table 1 Characteristics of the MHH BC cohort number percent cases histology IDBC ILBC others 6 3 pt status pt1

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1 Supplemental Data Table 1 Characteristics of the MHH BC cohort number percent cases histology IDBC ILBC others 6 3 pt status pt pt pt pt ptx 1 1 pn status pn pn pnx histological grade G G G ER positive negative PR positive negative AR positive negative n.a HER2 0, (FISH-neg.) p53 positive negative BCL2 positive negative CK5/14 positive negative 15 8 E-cadherin positive negative EGFR positive negative 2 1 Ki67 <5%, 5% %, 15% %, 25% %, 35% %, >40% AP-2 negative positive

2 Supplemental Data Table 2 Characteristics of the WSG PlanB BC cohort (limited to ER+/HER2- cases) number percent cases histology IDBC ILBC pt status pt pt pt pt ptx pn status pn pn pn pn histological grade G G G PR positive negative n.a Ki67 <5%, 5% %, 15% %, 25% %, 35% %, >40% 77 3 n.a ODX RS > n.a AP-2 negative positive

3 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 NMRIxC57BL/6 adult normal lactating Balb/c adult 30 day post weaning normal, involution Balb/c adult 50 day post weaning normal, involution Balb/c (T1) WAP sv40-t-ag Wsv40-T-ag, involution, 30 pw ductal carcinoma in situ Balb/c (T1) WAP sv40-t-ag Wsv40 induced murine mammary carcinoma T1 ductal carcinoma Balb/c WAP Cre Pik3CA H1047R Wcre; Pik3CA H1047R adenoasquamous carcinoma Balb/c WAP Cre Pik3CA H1047R Wcre; Pik3CA H1047R adenocarcinoma Balb/c MMTV Cre Pik3CA H1047R MMTVcre; Pik3CA H1047R adenomyoepithelioma FVB/N WAP Cre Trp53 Wcre-het; Trp53 F/F ; Cdh1 F/+ adenocarcinoma or Wcre-het; Trp53 F/F FVB/N WAP Cre Trp53 Wcre-het; Trp53 F/F ; Cdh1 F/+ solid carcinoma or Wcre-het; Trp53 F/F FVB/N WAP Cre Trp53 and Cdh1 Wcre-het; Trp53 F/F ; Cdh1 F/F, solid carcinoma 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 or Wcre-het; Trp53 F/+ ; Cdh1 F/F FVB/N WAP Cre Trp53 and Cdh1 Wcre-het; Trp53 F/F ; Cdh1 F/F metastasis or Wcre-het; Trp53 F/+ ; Cdh1 F/F FVB/N WAP Cre Cdh1 and Pten WCre;Cdh1 F/F ; Pten F/F lobular carcinoma total

4 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+, very strong nuclear staining > 90 % of tumor cells semiquantitative, , 25

5 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, , 25

6 Supplemental Data Table 6 AP-2 expression in human embryonic tissues mouse embryo human embryo selected anatomical day 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 + +

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