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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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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
DISCLOSURES • no conflicts of interest • no off-label uses discussed
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
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.
NSABP B-18 Schema Operable breast cancer Randomization AC x 4 surgery surgery AC x 4 Tam x 5 Yrs
pCR Rate Per Treatment in NSABP B-27 Bear HD, et al. J Clin Oncol 2003;21: 4165-4174
Survival Better If pCR Achieved B-18 (neoadjuvant AC) B-27 (all patients) Rastogi P, et al. J Clin Oncol 2008;26:778-785.
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.
Neo-ALTTO Complete Pathologic Response Proportions de Azambuja E et al. Lancet Oncology 2014;15:1132-1146
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.
NeoSphere Complete Pathologic Response Proportions Gianni L et al. Lancet Oncology 2012;13:25-32
TRYPHAENA Complete Pathologic Response Proportions Schneeweiss A et al. Ann Oncol 2013;24:22788-2284
CALGB 40603 “Triple-Negative” Breast Cancer NST Sikov, W et al. J Clin Oncol 2014 (online)
CALGB 40603 “Triple-Negative” Breast Cancer NST Sikov, W et al. J Clin Oncol 2014 (online)
CALGB 40603 “Triple-Negative” Breast Cancer NST Sikov, W et al. J Clin Oncol 2014 (online)
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
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.
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.