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Neoadjuvant SystemicTreatment Strategies for Breast Cancer

Neoadjuvant SystemicTreatment Strategies for Breast Cancer. Donald W. Northfelt, MD, FACP Professor of Medicine Mayo Clinic College of Medicine Associate Medical Director, Breast Clinic Mayo Clinic Arizona northfelt.donald@mayo.edu. DISCLOSURES. no conflicts of interest

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Neoadjuvant SystemicTreatment Strategies for Breast Cancer

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  1. NeoadjuvantSystemicTreatment Strategies for Breast Cancer Donald W. Northfelt, MD, FACP Professor of Medicine Mayo Clinic College of Medicine Associate Medical Director, Breast Clinic Mayo Clinic Arizona northfelt.donald@mayo.edu

  2. DISCLOSURES • no conflicts of interest • no off-label uses discussed

  3. Historical Treatment Paradigm for Breast Cancer • Radical surgery • Radical surgery + post-operative systemic therapy (improve long term disease free survival) • Limited surgery +/- radiotherapy + post-operative systemic therapy • Pre-operative systemic therapy to facilitate even more limited surgery • Curative systemic therapy

  4. Rationale for Neoadjuvant Systemic Therapy • to improve surgical options • to determine the response to NST (and abandon ineffective therapy?) • to obtain long-term disease-free survival (conventional post-operative adjuvant therapy addresses only the third objective) Kauffman, et al. J Clin Oncol 2006;24:1940-1949.

  5. NSABP B-18 Schema Operable breast cancer Randomization AC x 4 surgery surgery AC x 4 Tam x 5 Yrs

  6. NSABP B-27 Schema

  7. Rastogi P, et al. J Clin Oncol 2008;26:778-785.

  8. Rastogi P, et al. J Clin Oncol 2008;26:778-785.

  9. Rastogi P, et al. J Clin Oncol 2008;26:778-785.

  10. pCR Rate Per Treatment in NSABP B-27 Bear HD, et al. J Clin Oncol 2003;21: 4165-4174

  11. Survival Better If pCR Achieved B-18 (neoadjuvant AC) B-27 (all patients) Rastogi P, et al. J Clin Oncol 2008;26:778-785.

  12. Trend Toward Improved Survival with NST - B18 age < 50: DFS HR 0.85 P = .09 OS HR 0.81 P = .06 B-18 (neoadjuvant AC) Rastogi P, et al. J ClinOncol2008;26:778-785.

  13. HER2 + Breast CancerNeoadjuvant Systemic Therapy

  14. HER2+ Breast Cancer NST

  15. Neo-ALTTO Complete Pathologic Response Proportions de Azambuja E et al. Lancet Oncology 2014;15:1132-1146

  16. NeoSphere StudySchema R THP q 3w x 4 (n = 107) HP q 3w x 4 (n = 107) TP q 3w x 4 (n = 96) TH q 3w x 4 (n = 107) Surgery Surgery Surgery Surgery H q 3w x 13 + FEC q 3w x 3 H q 3w x 13 + T q3w x 4 FEC q 3w x 3 H q 3w x 13 + FEC q 3w x 3 H q 3w x 17 + FEC q 3w x 3 T = Docetaxel, H = Trastuzumab, P = Pertuzumab F = 5-fluorouracil, E = Epirubicin, C = Cyclophosphamide Gianni L et al. Proc SABCS 2010;Abstract S3-2.

  17. NeoSphere Complete Pathologic Response Proportions Gianni L et al. Lancet Oncology 2012;13:25-32

  18. TRYPHAENA Complete Pathologic Response Proportions Schneeweiss A et al. Ann Oncol 2013;24:22788-2284

  19. “Triple Negative”Breast CancerNeoadjuvant Systemic Therapy

  20. CALGB 40603 “Triple-Negative” Breast Cancer NST Sikov, W et al. J Clin Oncol 2014 (online)

  21. CALGB 40603 “Triple-Negative” Breast Cancer NST Sikov, W et al. J Clin Oncol 2014 (online)

  22. CALGB 40603 “Triple-Negative” Breast Cancer NST Sikov, W et al. J Clin Oncol 2014 (online)

  23. Neoadjuvant Endocrine Therapy • safety established • clinical responses frequent • proportion of patients undergoing breast conservation can be increased • pCR is rare (< 5% of patients) • efficacy: AIs > tamoxifen • decline in Ki67 may predict outcome • optimal duration of therapy uncertain

  24. Selection of Patients for Neoadjuvant Systemic Therapy • pCR = lower recurrence risk • factors associated with a higher likelihood of pCR: • tumor size (small > large) • histology (ductal > lobular) • intrinsic subtype (basal, HER2 > luminal) • hormone receptor status (ER­- > ER+) • grade (high > low) Gralow JR et al. J ClinOncol 2008;22:814-819.

  25. CONCLUSIONS • Neoadjuvant systemic therapy is appropriate (preferred?) for any patient for whom adjuvant systemic therapy is appropriate. • Increasingly effective neoadjuvant strategies are being developed. • Importance of pathologic complete response may vary with breast cancer subtype.

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