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The use of genomic medicine in breast cancer treatment, focusing on the recurrence score developed to stratify the risk of relapse and need for chemotherapy. The recurrence score is based on the expression and/or genetic abnormalities of multiple genes in the tumor, and can be determined through quantitative reverse transcription pcr (qrt-pcr) of rna from formalin fixed paraffin-embedded tumor tissue. The recurrence score is a continuous predictor of recurrence and can be used to determine prognosis and risk.
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TK EGFR/HER-2 HER-3/HER-2 HER-4/HER-
TKTK TK TK
Ligands^ HER-3 Ligands^ HER-
TK
Ligands^ EGFR
SOS GRB RAS MEK MAPK
PI3K AKT
The First Therapy Based on Tumor Genotype HER2/Neu amplification
Quantitative Reverse Transcription PCR mRNA 5’ 3’
cDNA^ 5’ (^) 3’ 3’5’ 3’ (^) 5’ (^) 3’ 5’
Bind Molecular Probe
R Q
Reverse Transcribe RNA
Molecular Probe Perform PCR 3’ (^) 3’ 5’ R
Q Probe cleavage and release of reporter Multiple Rounds of PCR
R^ R^ R R
R
PROLIFERATION Ki- STK Survivin Cyclin B MYBL
OTHER GSTM CD BAG
HER GRB HER
INVASION Stromolysin 3 Cathepsin L
ESTROGEN ER PR Bcl SCUBE
REFERENCE Beta-actin GAPDH RPLPO GUS TFRC
mRNA Targets
Prognosis
RS≤ RS 18- RS≥
Score % Pts RR at 10y 51 22 27
**6.
30.**
Low (338) Intermediate (149) High (181)
Risk
p<0.
A:<= 1cm B:1.1-2.0cmClinical.Tumor.Size C:2.1-4.0cm D:>= 4.1cm
0
20
40
60
80
100
Recurrence.Score Recurrence Score
≤ 1 cm 1.1 - 2 cm 2.1 - 4 cm (^) > 4 cm Clinical Tumor Size
A:<= 1cm B:1.1-2.0cmClinical.Tumor.Size C:2.1-4.0cm D:>= 4.1cm
0
20
40
60
80
100
Recurrence.Score Recurrence Score
≤ 1 cm 1.1 - 2 cm 2.1 - 4 cm (^) > 4 cm Clinical Tumor Size
A:<= 1cm B:1.1-2.0cmClinical.Tumor.Size C:2.1-4.0cm D:>= 4.1cm
0
20
40
60
80
100
Recurrence.Score Recurrence Score
≤ 1 cm 1.1 - 2 cm 2.1 - 4 cm (^) > 4 cm Clinical Tumor Size
Tumor Size
Oncotype Risk Group
HER2/Neu Amplified
HER2/Neu Not Amplified
Total Low Risk 0 334 334
Intermediate Risk 5 142 147
High Risk 50 129 179 Total 55 605 660
HER2/Neu Amplification