Oncotype Dx Mammaprint

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Oncotype Dx Mammaprint

  1. 1. <ul><li>OncotypeDX </li></ul><ul><li>Mammaprint </li></ul><ul><li>Dr. Jiveliouk Irina </li></ul>
  2. 2. Breast Cancer Early Locally advanced Metastatic
  3. 3. Early breast cancer 85 with No Distant Recurrence 15 with Distant Recurrence 100 women ; N - , ER+ After Surgery & Tamoxifen
  4. 4. Breast Cancer - Survival Pre-menopausal patients, lymph node negative time (years) survival ~30% die of breast cancer ~70% survive breast cancer
  5. 5. Prognistic and Predictive factors <ul><li>Lymph node involvement </li></ul><ul><li>Age </li></ul><ul><li>Tu size </li></ul><ul><li>Grade </li></ul><ul><li>Hormonal status </li></ul><ul><li>Her 2 status </li></ul>
  6. 6. Early Breast cancer <ul><li>Surgery </li></ul><ul><li>Chemotherapy </li></ul><ul><li>Radiotherapy </li></ul><ul><li>Hormonal Therapy </li></ul><ul><li>Biologic Therapy </li></ul>
  7. 7. Early breast cancer 85 with No Distant Recurrence 15 with Distant 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
  8. 8. Oncotype DX 21-gene recurrence score
  9. 9. PROLIFERATION Ki-67 STK15 Survivin Cyclin B1 MYBL2 ESTROGEN ER PR Bcl2 SCUBE2 INVASION Stromelysin 3 Cathepsin L2 HER2 GRB7 HER2 BAG1 GSTM1 REFERENCE Beta-actin GAPDH RPLPO GUS TFRC CD68 Paik et al. N Engl J Med. 2004;351:2817-2826. 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: + 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 RS =
  10. 10. Results: Population distribution by Oncotype DX risk group A Multigene Assay to Predict Recurrence of Tamoxifen-Treated, Node-Negative Breast Cancer Paik .S. et al. N Engl J Med 2004 ;351:2817-26 Intermed. risk 27.0% Low risk 51.0% High risk 22.0%
  11. 11. Distant Recurrence-Free Survival (%) P < 0.00001 Paik .S. et al. N Engl J Med 2004 ;351:2817-26 93% 69% All patients Low Risk (RS < 18) Years 100 0 20 40 60 DRFS (%) 80 0 2 6 10 4 8 12 16 14 Intermediate Risk (RS 18 - 30) High Risk (RS  31)
  12. 12. Recurrence Score Low RS < 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 2004 ;351:2817-26 40 35 30 25 20 15 10 5 0 0 5 10 15 20 25 30 35 40 45 50 Recurrence Score Rate of Distant Recurrence at 10 years 95% C.I. Recurrence Rate
  13. 13. Case 1 <ul><li>41-year-old patient with 2.1-cm tumor </li></ul><ul><li>Menopausal Status: Premenopausal </li></ul><ul><li>Tumor Type: IDC </li></ul><ul><li>ER and PR Status (IHC): Positive </li></ul><ul><li>HER2/neu Status (IHC): Negative </li></ul><ul><li>Histologic Grade: 1 </li></ul><ul><li>Lymph Node Status: Negative </li></ul>
  14. 14. 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%)
  15. 15. Case 2 <ul><li>Age 62 </li></ul><ul><li>T= 1.8cm </li></ul><ul><li>N=0 </li></ul><ul><li>ER ++, PR - </li></ul><ul><li>HER2 = +++ </li></ul><ul><li>Grade 2 </li></ul>
  16. 16. Onco type DX ™ - TAILORx - Study Design Onco type 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) <ul><li>Stratify </li></ul><ul><li>Tumor Size ≤2.0 cm vs. ≥ 2.1 cm </li></ul><ul><li>Post menopausal vs. Pre-or Peri-menopausal </li></ul><ul><li>Planned chemotherapy: Taxane-containing (i.e. paclitaxel, docetaxel) vs. </li></ul><ul><li>Non-taxane-containing </li></ul>Arm A Hormonal Therapy Randomize Arm D Chemotherapy Plus Hormonal Therapy Arm B Hormonal Therapy Arm C Chemotherapy Plus Hormonal Therapy
  17. 17. Conclusions: Onco type DX TM <ul><ul><li>Low RS associated with minimal chemotherapy benefit </li></ul></ul><ul><ul><li>High RS associated with large chemotherapy benefit </li></ul></ul><ul><li>The Onco type 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. </li></ul>
  18. 18. <ul><li>Mammaprint 70-gene profile </li></ul><ul><li>Oncotest-Teva </li></ul>
  19. 19. Old versus new diagnostics of cancer: from microscope to microarray High grade Low grade High risk Low risk MammaPrint
  20. 20. Prognosis Classifier for Breast Cancer based on Genomic Profiling Good signature Poor signature threshold Rows: 70 significant prognosis genes Columns: tumor samples Threshold set with 10% false negatives 91% sensitivity; 73% specificity Van ‘t Veer et al Nature 415, p530-536, 2002 Metastases: white = +
  21. 21. A Gene-Expression Signature as a Predictor of Survival in Breast Cancer Metastasis Free Survival Overall survival H.R. = 5.1 95% CI = 2.9 - 9.0 P < 0.001 H.R. = 8.6 95% CI = 4 - 19 P < 0.001 van de Vijver M.J. et al. N Eng J Med 2002 ;347(25):1999-2009. Results: all patients Good signature Poor signature Years 100 0 20 40 60 % patients metastasis free 80 0 2 4 6 8 10 12 Years 100 0 20 40 60 Overall survival (%) 80 0 2 4 6 8 10 12 85.2% 50.6% 94.5% 54.6%
  22. 22. Profiling vs. St Gallen selection (LN0, <53) <ul><li>improved prediction. </li></ul><ul><li>Significantly less women classified as having a bad prognosis </li></ul>van de Vijver M.J. et al. N Eng J Med 2002 ;347(25):1999-2009. St Gallen St Gallen: 15% in low risk 85% in high risk Profile Profiling: 40% in good profile 60 % in poor profile
  23. 23. MINDACT Design (Microarray in Node-Negative Disease May Avoid Chemotherapy Trial) All hormone responsive patients receive endocrine therapy Clinical pathological AND 70-gene signature HIGH risk Clinical pathological AND 70-gene signature LOW risk 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% Use Clin-Path risk to decide on adjuvant chemotherapy or not Use 70-gene risk to decide on adjuvant chemotherapy or not No chemotherapy chemotherapy R
  24. 24. <ul><li>Oncotype </li></ul><ul><li>Early breast cancer </li></ul><ul><li>Hormonal receptor positive </li></ul><ul><li>Her 2 Negative </li></ul><ul><li>Mammaprint </li></ul><ul><li>Early node negative breast cancer </li></ul>

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