OncotypeDX Mammaprint
Dr. Jiveliouk Irina
Breast Cancer
Early
Locally advanced
Metastatic
85 with No Distant Recurrence
15 withDistant Recurrence
100 women ; N - , ER+After Surgery & Tamoxifen
Early breast cancer
time (years)
surv
ival
~30% die of breast cancer
~70% survive breast cancer
Breast Cancer - Survival Pre-menopausal patients, lymph
node negative
Prognistic and Predictive factors
• Lymph node involvement
• Age
• Tu size
• Grade
• Hormonal status
• Her 2 status
Early Breast cancer
• Surgery
• Chemotherapy• Radiotherapy• Hormonal Therapy• Biologic Therapy
85 with No Distant Recurrence
15 withDistant Recurrence
100 women ; N - , ER+After Surgery & Tamoxifen
“at least 85 percent of patients would be over treated with chemotherapy if it were offered to everyone.”
Paik .S. et al. N Engl J Med 2004;351:2817-26
Early breast cancer
Oncotype DX 21-gene recurrence score
PROLIFERATIONKi-67
STK15Survivin
Cyclin B1MYBL2
ESTROGENERPR
Bcl2SCUBE2
INVASIONStromelysin 3Cathepsin L2
HER2GRB7HER2
BAG1 GSTM1
REFERENCEBeta-actinGAPDHRPLPO
GUSTFRC
CD68
Paik et al. N Engl J Med. 2004;351:2817-2826.
RS = + 0.47 x HER2 Group Score - 0.34 x ER Group Score + 1.04 x Proliferation Group Score+ 0.10 x Invasion Group Score + 0.05 x CD68- 0.08 x GSTM1- 0.07 x BAG1
16 cancer genes and 5 reference genes make up the 16 cancer genes and 5 reference genes make up the Oncotype DX gene panel. The expression of these genes is Oncotype DX gene panel. The expression of these genes is used to calculate the recurrence score:used to calculate the recurrence score:
16 cancer genes and 5 reference genes make up the 16 cancer genes and 5 reference genes make up the Oncotype DX gene panel. The expression of these genes is Oncotype DX gene panel. The expression of these genes is used to calculate the recurrence score:used to calculate the recurrence score:
Results: Population distribution by Oncotype DX risk group
A Multigene Assay to Predict Recurrence of Tamoxifen-Treated, Node-Negative Breast Cancer
Intermed. risk27.0%
Intermed. risk27.0%
Low risk51.0%
Low risk51.0%
Paik .S. et al. N Engl J Med 2004;351:2817-26
High risk22.0%
High risk22.0%
All patientsLow Risk (RS < 18)
Years
100
0
20
40
60
DR
FS
(%
)
80
0 2 6 104 8 12 1614
Intermediate Risk (RS 18 - 30)High Risk (RS 31)
P < 0.00001
Distant Recurrence-Free Survival (%)
Paik .S. et al. N Engl J Med 2004;351:2817-26
93%
69%
Recurrence Score
40
35
30
25
20
15
10
5
00 5 10 15 20 25 30 35 40 45 50
Recurrence Score
Rat
e o
f D
ista
nt
Rec
urr
ence
at
10 y
ears
95% C.I.
Recurrence Rate
LowRS < 18Rec. Rate = 6.8%C.I. = 4.0% - 9.6%
IntermediateRS 18 - 31Rec. Rate = 14.3%C.I. = 8.3% - 20.3%
HighRS 31Rec. Rate = 30.5%C.I. = 23.6% - 37.4%
Paik .S. et al. N Engl J Med 2004;351:2817-26
Case 1
•41-year-old patient with 2.1-cm tumor
•Menopausal Status: Premenopausal
•Tumor Type: IDC
•ER and PR Status (IHC): Positive
•HER2/neu Status (IHC): Negative
•Histologic Grade: 1
•Lymph Node Status: Negative
Recurrence score= 3
Patients with a Recurrence Score of 3 in clinical validation study had an Average Rate of Distance
Recurrence at 10 years of 4%(95% CI: 2%–6%)
Age 62 T= 1.8cm N=0 ER ++, PR- HER2 = +++ Grade 2
Case 2
Oncotype DX™ Assay
No Minimal Chemotherapy
Benefit Group
Recurrence Score <11
(~29% of Population)
Uncertain Chemotherapy
Benefit Group
Recurrence Score 11-25
(~44% of Population)
Established Chemotherapy
Benefit Group
Recurrence Score >25
(~27% of Population)
Stratify Tumor Size ≤2.0 cm vs. ≥ 2.1 cm Post menopausal vs. Pre-or Peri-menopausal Planned chemotherapy: Taxane-containing (i.e. paclitaxel, docetaxel) vs.
Non-taxane-containing
Arm A
Hormonal Therapy
Randomize
Arm DChemotherapy Plus
Hormonal Therapy
Arm B
Hormonal TherapyArm C
Chemotherapy Plus
Hormonal Therapy
Oncotype DX™ - TAILORx - Study Design
Conclusions: Oncotype DXTM
Low RS associated with minimal chemotherapy benefitHigh RS associated with large chemotherapy benefit
• The Oncotype DX Recurrence Score provides precise, quantitative information for individual patients on prognosis across and statistically independent of information on patient age, tumor size, and tumor grade.
Mammaprint 70-gene profile
Oncotest-Teva
High grade
Low grade
High riskLow riskMammaPrint
Old versus new diagnostics of cancer:from microscope to microarray
Prognosis Classifier for Breast Cancer based on Genomic Profiling
Good signature
Poor signature
threshold
Ro
ws:
70
sig
nif
ican
t p
rog
no
sis
gen
es
Columns: tumor samples
Threshold set with 10% false negatives91% sensitivity; 73% specificity
Van ‘t Veer et al Nature 415, p530-536, 2002
Metastases: white = +
St St Gallen
St Gallen:15% in low risk85% in high risk
Profile
Profiling:40% in good profile60 % in poor profile
Profiling vs. St Gallen selection (LN0, <53)
• improved prediction.
• Significantly less women classified as having a bad prognosis
van de Vijver M.J. et al. N Eng J Med 2002;347(25):1999-2009.
MINDACT Design (Microarray in Node-Negative Disease
May Avoid Chemotherapy Trial)
Use Clin-Path risk to decide on adjuvant
chemotherapy or not
Use 70-gene risk to decide on adjuvant
chemotherapy or not
All hormone responsive patients receive endocrine therapy
No chemotherapychemotherapy
Clinical pathological AND
70-gene signature
HIGH risk
Clinical pathological AND
70-gene signature
LOW risk
R
Discordant cases
Clin-Path HIGH risk 70-gene LOW risk
Clin-Path LOW risk 70-gene HIGH risk
Evaluate clinico-pathological risk (Adjuvant!) AND 70-gene signature risk
Buyse M et al, JNCI 2006
N=3300 55%
32%
n=1920
N=780
13%
OncotypeOncotype
Early breast cancerEarly breast cancer
Hormonal receptor positiveHormonal receptor positive
Her 2 NegativeHer 2 Negative
MammaprintMammaprint
Early node negative breast cancerEarly node negative breast cancer
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