Oncotype Dx Mammaprint

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%


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 (%)


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%


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


Established Chemotherapy

Benefit Group

Recurrence Score >25


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

Oncotype Dx Mammaprint

Health & Medicine

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