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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

Prognostic Factors in Breast Cancer; Many Identified; Examples: Node status Tumour size Histologic grade Estrogen receptor Progesterone receptor IGF-IR

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Page 1: Prognostic Factors in Breast Cancer; Many Identified; Examples: Node status Tumour size Histologic grade Estrogen receptor Progesterone receptor IGF-IR

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

Page 2: Prognostic Factors in Breast Cancer; Many Identified; Examples: Node status Tumour size Histologic grade Estrogen receptor Progesterone receptor IGF-IR

ERBB2GRB7TNF-receptor-associated factor 4TGFB1-induced anti-apoptotic factor 1

Cadherin 3Lamininkeratin 17keratin 5troponin ITGF beta 2GRO1 oncogene, alpha

CD36 antigen collagenglutathione peroxidase 3 plasmalipoprotein lipaseintegrin, alpha 7retinol-binding protein 4

Putative G-coupled receptorEstrogen receptortrefoil factor 3GATA-binding protein 3X-box binding protein 1LIV-1NAT1 arylamine

transferrin receptor p90V-myb homologintegral membrane transporterhydrolase conjugasenucleolar protein p40

•Nature 406:747-752,2000

•PNAS 98:10869-10874, 2001

Page 3: Prognostic Factors in Breast Cancer; Many Identified; Examples: Node status Tumour size Histologic grade Estrogen receptor Progesterone receptor IGF-IR

”Survival or RFS ”endpoints”

”Metastatic potential”

”Therapy effect”

”Growth rate”

Lymph node status

TP53 Mutations

Page 4: Prognostic Factors in Breast Cancer; Many Identified; Examples: Node status Tumour size Histologic grade Estrogen receptor Progesterone receptor IGF-IR

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

Page 5: Prognostic Factors in Breast Cancer; Many Identified; Examples: Node status Tumour size Histologic grade Estrogen receptor Progesterone receptor IGF-IR

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Page 6: Prognostic Factors in Breast Cancer; Many Identified; Examples: Node status Tumour size Histologic grade Estrogen receptor Progesterone receptor IGF-IR

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