Lisa A. Newman, M.D., M.P.H., F.A.C.S. Professor of Surgery Director, Breast Care Center

1. Management of the Axilla in Patients Receiving Neoadjuvant Chemotherapy (neoCTX) for Breast Cancer Lisa A. Newman, M.D., M.P.H., F.A.C.S. Professor of Surgery Director, Breast Care Center University of Michigan Ann Arbor, MI

2. Expanding BCS Eligibility: Neoadjuvant Systemic Therapy CTX Effect on Primary Tumor

3. Preop vs Postop CTX: Randomized Trials

4. Surgical Staging of the Axilla • Axillary Lymph Node Dissection • Morbidity: Lymphedema, Numbness, Shoulder dysfunction • Lymphatic Mapping & SLN Bx • Alternative surgical staging strategy; minimizes risks of axillary surgery without compromising staging/treatment • Goal: Replicate pathway of cancer cells from primary tumor to initial draining axillary lymph node(s)

5. Is SLN Bx Compatible with Neoadjuvant CTX Protocols?Should it be performed pre-; post-; or pre- and post-CTX? • What happens to intramammary lymphatics as the primary breast tumor enlarges? • Does chemotherapy have a uniform effect on all axillary nodal metastases? • Does chemotherapy alter lymphatic drainage patterns?

6. SLN ACCURACYINT2/T3 TUMORS • What happens to intramammary lymphatics as the primary breast tumor enlarges? • Are SLN non-identification and false negative rates higher in cases of bulky breast tumors?

7. CTX EFFECTON AXILLARY METASTASES • Inferential Evidence: Decreased rates of node-positive disease in pts treated with neoadjuvant CTX • NSABP B-18 • Direct Evidence: Studies of pts with node-pos disease (documented by sono-guided FNA Bx) treated with neoadjuvant CTX: • 23-33% converted to node-negative status on post-CTX axillary lymph node dissection • Newman et al, Ann Surg Onc 2002 • Rouzier et al, JCO 2002 • Kuerer et al, Ann Surg 1999

8. SLN BXAFTER NEOADJUVANT CTX

9. SLN BX PRIORTONEOADJUVANT CTX

10. ADVANTAGES OF PRE-neoCTX VS. POST-neoCTX SLN BX

11. UNIVERSITYOF MICHIGANNEOCTX PROGRAM Comprehensive pre- and post- Neoadjuvant CTX axillary evaluation • Baseline axillary ultrasound • With sono-guided FNA-Bx of any suspicious nodes • Baseline SLN Bx in sono-neg pts • After completion of neoCTX: • Pre-CTX node-neg pts → → No further axillary surgery • Pre-CTX node-pos pts → → SLN Bx + cALND

12. Rationale for SLN Bx after Negative Axillary Ultrasound: Risk of False Negative Imaging • University of Michigan • Growney et al, SSO 2009 • 121 node-positive cases • Nodal mets documented by sono FNA in 88 (73%) and by SLN biopsy in 33 (27%) • Follow-up SLN necessary for accurate staging in ultrasound-negative cases

13. UM Approach to NeoCTX and Axillary Staging Pre- and post-CTX staging allows stratification of pts into 3 distinct categories • Pts presenting with node-neg disease • Pts presenting with node-pos disease, downstaged to pN-0 • Pts presenting with node-pos disease that is chemoresistant

14. Is it necessary to document the pathologic axillary status prior to delivery of neoadjuvant chemotherapy?

15. NSABP B-18: Patterns of Locoregional Failure • Neoadjuvant vs. Adjuvant AC • Stages I-III • Lumpectomy patients received breast XRT • Mastectomy patients received no chest wall or regional XRT Operable Breast Cancer Stratification • Age • Clinical Tumor Size • Clinical Nodal Status Surgery AC x 4 Surgery AC x 4 Tamoxifen X 5 years for pts > 50 after completion of chemo Fisher B. et al: JCO 1997, JCO 1998; Wolmark N. et al: JNCI 2001

16. NSABP B-18:PREDICTORSOF LRF B-18 Data suggest that post-CTX nodal status is reliable indicator of pts likely to benefit from locoregional or postmastectomy XRT However: -Small sample size of post-CTX node-negative cases -Unknown: LRF rates among pts that started out pathologically node-negative compared to those that were downstaged to node-negativity

17. UM Neoadjuvant CTX Experience • N= 161 neoadjuvant chemotherapy cases • Median age at diagnosis 49 years Mean tumor size at presentation 45.0 mm • Median follow-up 38.1 months • Relapse rate at median follow-up 21.7% • 35 patients • 17 Local Recurrences • 28 Distant Recurrences Kilbride et al, Ann Surg Onc 2008

18. Outcome by Axillary Lymph Node Response

19. Use of regional radiation (PMRT or breast + nodal fields) in downstaged group 12.5% p=0.33 3.6%

20. UM Approach to NeoCTX and Axillary Staging • Pre- and post-CTX staging allows stratification of pts into 3 distinct categories • Pts presenting with node-neg disease • Pts presenting as node-pos, downstaged to pN-0 • Pts presenting as node-pos disease, chemoresistant • Sequential use of lymphatic mapping offers promise of minimizing number of cases subjected to ALND

21. UM: 54 Cases of Node-Pos Breast Cancer Undergoing SLN Bx & Completion ALND after Neoadjuvant CTX Non-identification of post-CTX SLN in 1/54 cases (2%) Newman E et al Ann Surg Onc 2007 The Future: Abandon completion ALND in cases with a neg post-CTX SLN

22. ACOSOG Z1071 Study Schema Phase II Study Evaluating the Role of Sentinel Lymph Node Surgery and Axillary Lymph Node Dissection Following Preoperative Chemotherapy in Women with Node Positive Breast Cancer Accrual Target: 550 patients

23. Summary • Neoadjuvant chemotherapy (neoCTX) improves eligibility for breast-conserving surgery • Optimal strategy for integrating lymphatic mapping and neoadjuvant CTX remains undefined • Accuracy of sentinel lymph node biopsy not yet optimally-defined when performed after neoCTX • SLN biopsy prior to neoCTX requires additional surgical procedure and anesthetic exposure • Combination of pre- and post- neoCTX axillary staging provides maximal information regarding CTX response and is important for planning XRT

24. University of Michigan Health Center MUCHAS GRACIAS POR SU ATENCION!!!!