OncotypeDX

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• OncotypeDX
• Mammaprint
• Dr. Jiveliouk Irina
• 18.06.2008

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Breast Cancer

• Early
• Locally advanced
• Metastatic

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Early breast cancer
100 women N - , ERAfter Surgery Tamoxifen
85 with No Distant Recurrence
15 with Distant Recurrence
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Breast Cancer - Survival Pre-menopausal
patients, lymph node negative
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Prognistic and Predictive factors

• Lymph node involvement
• Age
• Tu size
• Grade
• Hormonal status
• Her 2 status

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Early Breast cancer

• Surgery
• Chemotherapy
• Radiotherapy
• Hormonal Therapy
• Biologic Therapy

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Early breast cancer
100 women N - , ERAfter Surgery Tamoxifen
85 with No Distant Recurrence
15 with Distant Recurrence
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 20043512817-26
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Oncotype DX 21-gene recurrence score
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16 cancer genes and 5 reference genes make up the
Oncotype DX gene panel. The expression of these
genes is used to calculate the recurrence score
PROLIFERATION Ki-67 STK15 Survivin Cyclin B1 MYBL2
ESTROGEN ER PR Bcl2 SCUBE2
BAG1
GSTM1
CD68
HER2 GRB7 HER2
INVASION Stromelysin 3 Cathepsin L2
REFERENCE Beta-actin GAPDH RPLPO GUS TFRC
Paik et al. N Engl J Med. 20043512817-2826.
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A Multigene Assay to Predict Recurrence of
Tamoxifen-Treated, Node-Negative Breast Cancer
Results Population distribution by Oncotype DX
risk group
Paik .S. et al. N Engl J Med 20043512817-26
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Distant Recurrence-Free Survival ()
93
P lt 0.00001
69
Paik .S. et al. N Engl J Med 20043512817-26
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Recurrence Score
Low RS lt 18 Rec. Rate 6.8 C.I. 4.0 - 9.6
Intermediate RS 18 - 31 Rec. Rate 14.3 C.I.
8.3 - 20.3
High RS ? 31 Rec. Rate 30.5 C.I. 23.6 -
37.4
Paik .S. et al. N Engl J Med 20043512817-26
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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

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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 26)
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Case 2

• Age 62
• T 1.8cm
• N0
• ER , PR-
• HER2
• Grade 2

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Oncotype DX - TAILORx - Study Design
Oncotype DX Assay
No Minimal Chemotherapy Benefit Group Recurrence
Score lt11 (29 of Population)
Uncertain Chemotherapy Benefit Group Recurrence
Score 11-25 (44 of Population)
Established Chemotherapy Benefit
Group Recurrence Score gt25 (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

Randomize
Arm D Chemotherapy Plus Hormonal Therapy
Arm C Chemotherapy Plus Hormonal Therapy
Arm A Hormonal Therapy
Arm B Hormonal Therapy
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Conclusions Oncotype DXTM

• Low RS associated with minimal chemotherapy
  benefit
• High 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.

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• Mammaprint 70-gene
  profile
• Oncotest-Teva

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Old versus new diagnostics of cancerfrom
microscope to microarray


High grade
Low grade
High risk
Low risk
MammaPrint
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Prognosis Classifier for Breast Cancer based on
Genomic Profiling
Columns tumor samples
Rows 70 significant prognosis genes
Good signature
threshold
Poor signature
Threshold set with 10 false negatives 91
sensitivity 73 specificity
Metastases white
Van t Veer et al Nature 415, p530-536, 2002
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A Gene-Expression Signature as a Predictor of
Survival in Breast Cancer
Results all patients
Metastasis Free Survival
Overall survival
H.R. 8.6 95 CI 4 - 19 P lt 0.001
H.R. 5.1 95 CI 2.9 - 9.0 P lt 0.001
van de Vijver M.J. et al. N Eng J Med
2002347(25)1999-2009.
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Profiling vs. St Gallen selection (LN0, lt53)

• improved prediction.
• Significantly less women classified as having a
  bad prognosis

van de Vijver M.J. et al. N Eng J Med
2002347(25)1999-2009.
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MINDACT Design (Microarray in Node-Negative
Disease May Avoid Chemotherapy Trial)
Evaluate clinico-pathological risk (Adjuvant!)
AND 70-gene signature risk
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N780 13
N3300 55
Discordant cases Clin-Path HIGH risk 70-gene
LOW risk Clin-Path LOW risk 70-gene HIGH risk
Clinical pathological AND 70-gene
signatureHIGH risk
Clinical pathological AND 70-gene signatureLOW
risk
n1920
All hormone responsive patients receive endocrine
therapy
Buyse M et al, JNCI 2006
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• Oncotype
• Early breast cancer
• Hormonal receptor positive
• Her 2 Negative
• Mammaprint
• Early node negative breast cancer