1. Prognostic Factors in Breast Cancer; Many Identified; Examples: Node status Tumour size Histologic grade Estrogen receptor Progesterone receptor IGF-IR Marrow micromets ErbB-2 expression EGF-R TP53 mutations Cathepsin D Telomerase activity PAI-1 level

2. ERBB2 GRB7 TNF-receptor-associated factor 4 TGFB1-induced anti-apoptotic factor 1 Cadherin 3 Laminin keratin 17 keratin 5 troponin I TGF beta 2 GRO1 oncogene, alpha CD36 antigen collagen glutathione peroxidase 3 plasma lipoprotein lipase integrin, alpha 7 retinol-binding protein 4 Putative G-coupled receptor Estrogen receptor trefoil factor 3 GATA-binding protein 3 X-box binding protein 1 LIV-1 NAT1 arylamine transferrin receptor p90 V-myb homolog integral membrane transporter hydrolase conjugase nucleolar protein p40 Nature 406:747-752,2000 PNAS 98:10869-10874, 2001

3. ”Survival or RFS ”endpoints” ”Metastatic potential” ”Therapy effect” ”Growth rate” Lymph node status TP53 Mutations

4. Cell cycle Cyclins ( cyc D) and a cdk (like cdk4/cdk6) complex Acting in different phases of the cycle Influenced by inhibitors (p16, p21, p27, p57) Amplifications – mutations Influenced by upstream GF / Oncogenes Some genes involved in cell cycle control (sometimes at G1 as well as G2) also involved in apoptosis (p53) Therapy effects; growth arrest / apoptosis poorly understood

5. X1 X2 X3 X4 Y2 Y1 Z1 Z2 Z3 Y11 Y21 Z11 Z21 Z31 D1 D12 D2 D21 D22 D23 D3 D31 G1 G2 G3 G11 G111 G21 G31

6. X1 X2 X3 X4 Y2 Y1 Z1 Z2 Z3 Y11 Y21 Z11 Z21 Z31 D1 D12 D2 D21 D22 D23 D3 D31 G1 G2 G3 G11 G111 G21 G31 Y1 Y2 Y3