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Enfermedad Triple Negativa: ¿hacia dónde vamos?

Enfermedad Triple Negativa: ¿hacia dónde vamos?. Cáncer de Mama Avanzado. Ignasi Tusquets Trías de Bes Hospital del Mar Barcelona. Triple Negativo. Triple Negativo. RE (-). RP (-). C-erbB-2 (-). Triple Negativo. TNBC = ER- PR- HER2-.

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Enfermedad Triple Negativa: ¿hacia dónde vamos?

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  1. Enfermedad Triple Negativa: ¿hacia dónde vamos? Cáncer de Mama Avanzado Ignasi Tusquets Trías de Bes Hospital del Mar Barcelona

  2. Triple Negativo

  3. Triple Negativo RE (-) RP (-) C-erbB-2 (-)

  4. Triple Negativo TNBC = ER- PR- HER2- “considered positive if there are at least 1% positive tumor nuclei in the sample” ASCO/CAP guideline JCO 2010.

  5. Triple Negativo

  6. Triple Negativo

  7. Triple Negativo

  8. pCR TN vs no-TN Rouzier, Clin Cancer Res 2005 Carey, SABC 2004 Keam, BMC Cancer 2007 Liedtke, JCO 2008 Huober, Breast Cancer Res Treat 2010

  9. Triple Negativo

  10. NEJM 363;20,2010

  11. Claudin Low = Claudins- Cadherin- CD44+ 5% de los cánceres de mama

  12. PERFIL IHQ DE CMTN RE (-) RP (-) C-erbB-2 (-)

  13. PERFIL IHQ de Basal-Like RE (-) RP (-) C-erbB-2 (-) EGFR (+) CK 5/6 (+) BLBC = ER- PR- HER2- EGFR+ CK5/6+

  14. IHQ – FISH EGFR BC: 16-36% TNBC: 50% Basal-like: 65-72%

  15. Anti-EGFR

  16. Ac Anti-EGFR

  17. Primary objective not met since ORR in patients treated with cetuximab plus cisplatin did not exceed 20% (p=0.5)

  18. “BRCAness”

  19. “BRCAness” • Baja expresión BRCA • Metilación del promotor BRCA • Mutación BRCA

  20. “BRCAness” • Baja expresión BRCA • Metilación del promotor BRCA • Mutación BRCA Fallo en el mecanismo de Recombinación Homóloga

  21. “BRCAness” • Baja expresión BRCA • Metilación del promotor BRCA • Mutación BRCA Fallo en el mecanismo de Recombinación Homóloga Disfunción en los mecanismos de reparación de DNA

  22. Ensayos con Platinos (Neoadyuvancia)

  23. Ensayos con Platinos (Neoadyuvancia)

  24. Ensayos con Platinos (Neoadyuvancia)

  25. Inhibidores PARP

  26. Inhibidores PARP • Olaparib • Iniparib • Veliparib • AG014699 • MK4827

  27. Célula normo-funcionante. Mecanismos de reparación Supervivenciacelular

  28. BRCAness Supervivenciacelular

  29. PARPi Muertecelular

  30. Tutt A. Lancet 2010

  31. OLAPARIB in TNBC and OC Overall response rate Karen Gelmon ASCO 2010

  32. Phase II TNBC Study: Treatment Schema RANDOMIZE Metastatic TNBC N = 120 BSI-201 (5.6 mg/kg, IV, d 1, 4, 8, 11) Gemcitabine (1000 mg/m2, IV, d 1, 8) Carboplatin (AUC 2, IV, d 1, 8) Gemcitabine (1000 mg/m2, IV, d 1, 8) Carboplatin (AUC 2, IV, d 1, 8) 21-Day Cycle RESTAGING Post-Cycle 2 & every 6-8 wks * Patients randomized to gem/carbo alone could crossover to receive gem/carbo + BSI-201 at disease progression O’Shaughnessy J. NEJM 2011 BiPar Sciences Confidential

  33. Median Progression-free Survival: 5.9 m vs 3.6 m O’Shaughnessy J. NEJM 2011

  34. Median Overall Survival: 12.3 m vs 7.7 m O’Shaughnessy J. NEJM 2011

  35. Phase III TNBC Study: RANDOMIZE Metastatic TNBC N = 520 BSI-201 (5.6 mg/kg, IV, d 1, 4, 8, 11) Gemcitabine (1000 mg/m2, IV, d 1, 8) Carboplatin (AUC 2, IV, d 1, 8) Gemcitabine (1000 mg/m2, IV, d 1, 8) Carboplatin (AUC 2, IV, d 1, 8) 21-Day Cycle RESTAGING Post-Cycle 2 & every 6-8 wks Primary Objective: OS and DFS Stratification: 1st, 2nd, 3rd line BiPar Sciences Confidential

  36. Ongoing clinical trials of targeted agents in metastatic TNBC

  37. F. Rojo. In press.

  38. F. Rojo. In press.

  39. mRNA expression Goçalves A. Breast Cancer Res Treat 2010.

  40. F. Rojo. In press.

  41. Antiangiogenicos

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