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Claudia Bighin IRCSS – AOU S . Martino – IST Genova

Highlights in the management of breast cancer How to improve the outcome of Triple-Negative Breast Cancer. Claudia Bighin IRCSS – AOU S . Martino – IST Genova. «From benchside to bedside ». Bed-side. Dissecting the Heterogeneity of TNBC. CK5/6, CK17.

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Claudia Bighin IRCSS – AOU S . Martino – IST Genova

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  1. Highlights in the management of breast cancerHow to improve the outcome of Triple-Negative Breast Cancer Claudia Bighin IRCSS – AOU S. Martino – IST Genova

  2. «From benchside to bedside»

  3. Bed-side

  4. Dissecting the Heterogeneity of TNBC CK5/6, CK17 Metzger-Filho et al, JCO 2012

  5. 76% of the TNBC had a BRCA1-like aCGH profile Lips et al, BJC 2013

  6. Good news from earlierstages?

  7. Cheang et al, ASCO 2009

  8. Cheang et al, ASCO 2009

  9. Cheang et al, ASCO 2009

  10. A-based vs CMF according to molecular subgroup (meta-analysis of 4 phase III trials) 1.06 *Triple negative disease A-based vs CMF HR: 0.77 95% CI 0.54-1.09 P value = 0.13 CMF 1 0.83 0.82 A-based 0.77* 0.67 Di Leo et al, Lancet Oncol 2011

  11. TNBC/Basal-like HER2 + Luminal B Luminal A Hugh J et al. JCO 2009

  12. Future perspective Joensuu et al, AnnOncol 2012

  13. SABCS 2012

  14. pCR predicts favourable outcome in TNBC The Paradox of higher sensitivity to neoadjuvant chemotherapy in poor prognosis subtype (TNBC) is explained by the high relapse among pts with residual disease Liedtke C, et al. J Clin Oncol 2008

  15. TNBC and pCR von Minckwitz et al, JCO 2012

  16. Ongoingneoadjuvant trial von Minckwitz et al, AnnOncol 2012

  17. Bevacizumab

  18. von Minckwitz et al, NEJM 2012

  19. Bear et al, NEJM 2012

  20. Phase II study: FECwPaclitaxel + Bevacizumab Clavarezza et al, The Breast 2013 (in press)

  21. ASCO 2013BreastCancerOral Session • Abstract #1003 • PrECOG0105: Finalefficacyresults from a phase II study of gemcitabine (G) and carboplatin (C) plus iniparib (BSI-201) asneoadjuvanttherapy for triple-negative (TN) and BRCA1/2 mutation-associatedbreastcancer.(Melinda L. Telli) • Abstract #1004 • A randomized phase II trial investigating the addition of carboplatin to neoadjuvant therapy for triple-negative and HER2-positive early breast cancer (GeparSixto).(Gunter Von Minckwitz)

  22. Median survival with distant metastases Luminal A: 2.2 yrs Luminal B: 1.6 yrs Luminal/HER2: 1.3 yrs HER2 enriched: 0.7 yrs Basal-like: 0.5 yrs 3,732 EBC diagnosed between 1986-1992 Basal-like treated with adj CT: 48%

  23. TNBC: Annual Hazard Rate of Distant Recurrence • Peak of recurrence • TN: 1 to 3 years • Non-TN: steady risk over time Dent R, et al. Clin Cancer Res 2007

  24. Foulkes et al, NEJM 2010

  25. Re-biospy?

  26. Cardoso et al, The Breast 2012

  27. TNBC: “…Cytotoxic chemotherapy remains the mainstay of treatment in thisgroup…» Cardoso et al, AnnOncol 2012

  28. Newlyapproveddrugs in TNBC 1 Rugo, SABCS 2008 2 O'Shaughnessy, ASCO 2011 3 Twelves, ESMO 2010

  29. Targetedtherapies

  30. BALI-1 Trial Baselga, SABCS 2010

  31. The difference between the arms was not significant (p=0.11) and the ORR in the cetuximab plus cisplatin arm did not exceed 20% (p=0.50; one-sided Z-test with a significance level of alpha/2=0.05), therefore the simultaneous null hypothesis could not be rejected. Baselga, SABCS 2010

  32. Baselga, SABCS 2010

  33. ORR < 20% Carey et al, JCO 2012

  34. Targetedtherapies

  35. Tutt et al, Lancet 2010

  36. Tutt et al, Lancet 2010

  37. O'Shaughnessy et al, NEJM 2011

  38. [TITLE] ORR 30 vs 34% O'Shaughnessy et al, ASCO 2011

  39. [TITLE] O'Shaughnessy et al, ASCO 2011

  40. Iniparib Olaparib Chuang et al, BCRT 2012

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