PERSPECTIVAS ACTUALES Y FUTURAS EN EL MANEJO DEL CÁNCER DE MAMA PRECOZ. PARTE II

1. PERSPECTIVAS ACTUALES Y FUTURAS EN EL MANEJO DEL CÁNCER DE MAMA PRECOZ. PARTE II Nuevo abordaje terapéutico de la neoadyuvancia Miquel Àngel Seguí Palmer

2. Nuevo abordaje terapéutico de la neoadyuvancia

3. Nuevo abordaje terapéutico de la neoadyuvancia Neoadjuvant Chemotherapy: Increase in Lumpectomy Rates

4. Nuevo abordaje terapéutico de la neoadyuvancia Re-excision for patients who underwent initial lumpectomy (Breast Cancers Between 2 and 4 cm Diameter) Any patient with a tumor greater than 2 cm should be considered for preoperative chemotherapy, even if the surgeon believes that an initial lumpectomy would be technically feasible Christy et al. Ann Surg Oncol 2009

5. Nuevo abordaje terapéutico de la neoadyuvancia

6. Nuevo abordaje terapéutico de la neoadyuvancia What we know Mauri et al. J Natl Cancer Inst. 2005 EBCTCG Overview. Oxford, September 2006

7. NSABP B-18 NSABP B-27 Nuevo abordaje terapéutico de la neoadyuvancia Effect of pCR on Overall Survival Rastogi et al. J Clin Oncol 2008

8. Nuevo abordaje terapéutico de la neoadyuvancia How should we define pCR pCR is a dichotomous endpoint: you either achieve pCR or you do not

9. Nuevo abordaje terapéutico de la neoadyuvancia How should we define pCR Disease-free Survival Overall Survival Mazouni et al. J Clin Oncol 2007

10. Nuevo abordaje terapéutico de la neoadyuvancia Residual Cancer Burden and Outcome Symmans et al. J Clin Oncol 2007

11. Nuevo abordaje terapéutico de la neoadyuvancia The pCR rate to neoadjuvant chemotherapy according to ER status

12. Nuevo abordaje terapéutico de la neoadyuvancia The pCR rate after neoadjuvant chemotherapy according to intrinsic molecular subtype *Immunohistochemical definition of molecular subtypes

13. Nuevo abordaje terapéutico de la neoadyuvancia Survival by pCR in TNBC Liedtke et al. J ClinOncol 2008

14. Nuevo abordaje terapéutico de la neoadyuvancia Survival by pCR in HER2+ BC TECHNO Trial pCR after Neoadjuvant Chemotherapy + Trastuzumab Treatment Predicts Survival Untch M et al. SABCS 2010

15. Nuevo abordaje terapéutico de la neoadyuvancia Progression-free survival by pCR in ER/PR+ BC Guarneri et al, JCO 2006 Montagna et al. Breast Cancer Res Treat 2010

16. Subset who received adjuvant hormone treatment Subset without adjuvant hormone treatment Nuevo abordaje terapéutico de la neoadyuvancia Residual Cancer Burden and Outcome Symmans et al. J Clin Oncol 2007

17. Nuevo abordaje terapéutico de la neoadyuvancia Pooled German Neoadjuvant Trials: Association of pCR with Treatment Characteristics* * after adjustment for age, tumor stage, grade, type, HR and HER2 status § effect as estimated for HER2-positive patients von Minckwitz et al. Breast Cancer Res Treat 2011

18. Nuevo abordaje terapéutico de la neoadyuvancia Pooled German Neoadjuvant Trials: Association of pCR with Treatment Characteristics von Minckwitz et al. Breast Cancer Res Treat 2011

19. Nuevo abordaje terapéutico de la neoadyuvancia Pros/Cons of Neoadjuvant Therapy

20. Nuevo abordaje terapéutico de la neoadyuvancia Should We Revisit the Paradigm of Preop vs. Postop Chemo?

21. Nuevo abordaje terapéutico de la neoadyuvancia Prat and Perou. Nature Medicine 2009

22. Nuevo abordaje terapéutico de la neoadyuvancia

23. Nuevo abordaje terapéutico de la neoadyuvancia Neoadjuvant Therapy Questions in Hormonally Sensitive BC

24. Nuevo abordaje terapéutico de la neoadyuvancia The pCR rate to neoadjuvant chemotherapy according to histology There is also evidence that breast-conserving surgery is more likely to be unsuccessful at achieving complete excision of the primary lesion

25. Nuevo abordaje terapéutico de la neoadyuvancia Chemotheraphy versus Hormone Therapy as Neoadjuvant Treatment in Luminal Breast Cancer: GEICAM 2006-03 • Even in luminal phenotypes, chemotherapy tends to be more effective than hormonal therapy in the neoadjuvant setting • Chemotherapy appears to be more effective than hormonal therapy in patients with Ki67 >10%, pre-menopausal and with high Allred score • Hormonal therapy appears to have similar efficacy to chemotherapy in patients with Ki67 ≤10% and post-menopausal Alba et al. ASCO 2010

26. Nuevo abordaje terapéutico de la neoadyuvancia ACOSOG Z1031 Ellis et al. SABCS 2010

27. Nuevo abordaje terapéutico de la neoadyuvancia ACOSOG Z1031 Ellis et al. SABCS 2010

28. Nuevo abordaje terapéutico de la neoadyuvancia Clinical Data from Neoadjuvant Studies Predict Adjuvant Outcomes

29. Nuevo abordaje terapéutico de la neoadyuvancia ACOSOG Z1031 Ki67 changes and Luminal Subtype (PAM 50) Ellis et al. SABCS 2010

30. Nuevo abordaje terapéutico de la neoadyuvancia ACOSOG Z1031 Ki67 changes and Luminal Subtype (PAM 50) Luminal A and Luminal B tumors are both endocrine responsive but Luminal A is enriched for PEPI-0 patients who may do sufficiently well on AI alone Ellis et al. SABCS 2010

31. Nuevo abordaje terapéutico de la neoadyuvancia No pCRs if Good 70-Gene Signature Straver et al. Breast Cancer Res Treat 2010

32. Nuevo abordaje terapéutico de la neoadyuvancia NSABP B-27 Gene Expression and Survival Paik SABCS 2010

33. Nuevo abordaje terapéutico de la neoadyuvancia Neoadjuvant Therapy Questions HER-2 Positive BC

34. Nuevo abordaje terapéutico de la neoadyuvancia Neoadjuvant Herceptin significantly improves pCR rates MDACC NOAH Buzdar et al. ASCO 2004 Gianni et al. ESMO 2007

35. Nuevo abordaje terapéutico de la neoadyuvancia Neoadjuvant anthracycline and trastuzumab for breast cancer: is concurrent treatment safe? Combined analysis of the cardiac events reported in three prospective, neoadjuvant studies with concurrent use of anthracyclines and trastuzumab in patients with HER2-positive breast cancer (MDACC, NOAH, GeparQuattro) Primary endpoint: incidence of CHF and cardiac dysfunction The concurrent use of an anthracycline based chemotherapy and trastuzumab (583 of 1765 patients) was associated with an increased risk of cardiac toxicity OR 1.95, 95% CI 1.6–3.29 44 cardiac events when trastuzumab was added to chemotherapy compared with 28 cardiac events in the chemotherapy only groups Bozovic-Spasojevic et al. Lancet Oncoll 2011

36. Nuevo abordaje terapéutico de la neoadyuvancia GeparQuinto Study Untch et al. SABCS 2010

37. Nuevo abordaje terapéutico de la neoadyuvancia GeparQuinto Study pCR (no invasive/non-invasive residual in breast & nodes) pCR according to subtypes Untch et al. SABCS 2010

38. Nuevo abordaje terapéutico de la neoadyuvancia NeoALTTO Study Baselga et al. SABCS 2010

39. 51.3% 46.9% Nuevo abordaje terapéutico de la neoadyuvancia NeoALTTO Study Baselga et al. SABCS 2010

40. Nuevo abordaje terapéutico de la neoadyuvancia NeoSphere Study Gianni et al. SABCS 2010

41. Nuevo abordaje terapéutico de la neoadyuvancia NeoSphere Study pCR (no invasive residual in breast) Gianni et al. SABCS 2010

42. Nuevo abordaje terapéutico de la neoadyuvancia Neoadjuvant Therapy Questions HER-2 Negative or Triple-Negative BC

43. Nuevo abordaje terapéutico de la neoadyuvancia ABCSG-24: a randomised phase III study comparing epirubicin, docetaxel and capecitabine to epirubicin and docetaxel as neoadjuvant treatment for EBC Pre-planned analysis to determine benefit of EDC in patients with TNBC breast cancer Steger et al. ESMO 2010

44. Nuevo abordaje terapéutico de la neoadyuvancia Capecitabine in the Treatment of Triple-Negative Early Breast Cancer Steger et al. ESMO 2010

45. Nuevo abordaje terapéutico de la neoadyuvancia Sequential taxane and anthracycline-containing neoadjuvant regimens: The sequential order impact Thiery-Vuillemin et al. The Breast 2011

46. Nuevo abordaje terapéutico de la neoadyuvancia Platinum Sensitivity in BRCA1+/TNBC • Neoadjuvant trials: • Retrospective trial suggests exquisite sensitivity in BRCA1+ • Prospective trial in TNBC less clear Byrski, JCO 2009; Silver JCO 2009; Ryan ASCO 2009

47. Nuevo abordaje terapéutico de la neoadyuvancia Differential Response of TNBC to Docetaxel and Carboplatin-Based Neoadjuvant Treatment pCR of the primary tumor in three types of breast cancer Chang et al. Cancer 2010

48. Nuevo abordaje terapéutico de la neoadyuvancia 2006−03

49. Nuevo abordaje terapéutico de la neoadyuvancia Neoadjuvant doxorubicin vs docetaxel in TNBC Antitumor activity in intrinsic subtypes Martin et al. ASCO 2010

50. Nuevo abordaje terapéutico de la neoadyuvancia Neoadjuvant Chemotherapy With or Without Bevacizumab: The GeparQuinto Study von Minckwitz et al. SABCS 2010