1. Time (days) A % Overall Survival Time (days) % Overall Survival SUPPLEMENTAL FIGURE 1 Legend: MMTV-Cre, n = 71 R26(Pik3ca), n = 285 R26(Stat3), n = 46 K-Ras(G12D), n = 10 R26(Pik3ca H1047R );MMTV-Cre, n = 112 R26(Stat3 C );MMTV-Cre, n = 30 R26(Pik3ca H1047R /Stat3 C );MMTV-Cre, n = 48 K-Ras(G12D);MMTV-Cre, n = 35 R26(Pik3ca H1047R );K-Ras(G12D);MMTV-Cre, n = 58 R26(Stat3 C );K-Ras(G12D);MMTV-Cre, n = 25 | = censored data B

2. ABC KA SC AME SC PDA AME SUPPLEMENTAL FIGURE 2 STC SC CAC SC

3. E545KNormal β-Actin Stat3 pY705 Erk1/2 pT202/204 42kDa 84kDa 42-4kDa H1047RRasE545K;RasH1047R;Ras SUPPLEMENTAL FIGURE 3 CACSTC SCC CAC Ras Stat3 C ;Ras A B

4. A) Relapse B) Survival Relapse free (%)Disease free survival (%) SUPPLEMENTAL FIGURE 4 PI3K+ Stat3 Pathways PI3K + Ras Pathways Stat3 + Ras Pathways PI3K + Stat3 + Ras Pathways PI3K+ Stat3 Pathways PI3K + Ras Pathways Stat3 + Ras Pathways PI3K + Stat3 + Ras Pathways Time (years)

5. A) Relapse (PI3K Pathway) C) Relapse (Stat3 Pathway) D) Death (Stat3 Pathway) Relapse free (%) B) Death (PI3K Pathway) Basal-like SUPPLEMENTAL FIGURE 5 Time (years)