2. Basic Concepts Sentinel node biopsy is at least as good for axillary assessment as ALND and probably superior. Standard path evaluation for ALND yields ~ 20% false negative. SLN eval yields ~ 5% false negative. Long term follow-up of sentinel node negative patients with no ALND has recurrence rates of 1.5% or less. Survival after SLN – with adjuvant Rx is superior to Historical NSABP standard ALND – with adjuvant rx, suggesting missed + nodes in old studies and improved data on modern SLN studies. Even with + sentinel node and standard BCT Rx axillary recurrence is rare. Axillary node dissection probably provides no benefit to overall survival.

3. Sentinel node: Next Level questions Settings: Peri- neoadjuvant chemo IBT Recurrence with prior axillary interventions

4. Post Neo-adjuvant Chemo Axillary Node Issues Is sentinel node ID possible in this setting? Is the sentinel node concept meaningful in this setting? i.e. => Will it change therapy/ Surgery, Chemo or Rad Rx? Will a positive sentinel node imply additional positive nodes? Can ALND be avoided if SLN Negative? Should SLN BX be done pre Neoadj Rx (instead or in addition)

5. Questions Should a positive sentinel node in the Axillary Node Dissection Group lead to more detailed study of additional nodes? Will it change Rx. If a sentinel node is positive and add levels to other nodes, + 20% pickup? If ALND “only” may miss mets. Two levels per node. SLN the Only + node ~50% It is the sentinel node “positive” by SLN protocol, remainder “negative” by standard protocol, that may be significant. May be missed if not ID.

6. Other Issues Sentinel node count may be lower post neoadjuvant Rx What is the correlation between in breast CPR and nodal CPR.

7. Le Bouedec, Geissler, et al 2006 74 pts T1T2T3N0N1 POST neo SLN 68/74 (92%) then ALND Mets in 30/68 (44%) i.e. Neg 56% False neg 14% But if clinically neg N0 pre RX then accuracy 100% and FN 0% In 32 N1 patients accuracy 83% FN 25%

8. Reitsamer, Peintinger, et al (2003) 30 Patients Stage II or III, Rx Neoadj Chemo Attempted SLN with completion ALND SLN 26 of 30 (86.7%) (could not ID SLN in 4 (13.3%) SLN accurate 25 of 26 (96.2%) 11 pts Neg SLN and Neg ALND 6 pts Pos SLN and Pos ALND 8 pts SLN pos and the only Pos node (~30%) 1 pt false-neg (1/15 = 6.7%)

9. Cohen, Breslin, et al (2000) 38 pts, stage II or III treated with neoadjuvant chemo SLN attempted then ALND If SLN neg then all other nodes 3 add’l levels + IHC SLN ID in 31 (82%) and accurate 28 (90%) 3 False neg 4 of 20 “neg” SLN with add’l studies + for occult mets (20%)

10. Kinoshita, Takasugi, et al, 2006 Post neo 77 pts Stage II and III Clinically node neg post Rx SLN then ALND SLN ID 72 of 77 (93.5%) 69 of 72 accurate (95.8%) 3 of 27 False Neg (11%)

11. Mamounas, Brown et al NSABP B-27 428 pts SLN then ALND SLN ID 89% with isotope +SLN the only + node in 56% (70 of 125) Of 218 Neg SLN nonsent + 15 => False neg 11%

12. POST-NEO SLN PTSSLN IDFalse Neg SLN Accurate SLN only+ Le Bouedec 2006 SL/ALND 74 PTs68 (92%) 14% If cN0 pre 0% 83% 100% Reitsamer 2003 SLN/ALND 3026 86% 25/26 96% 8/30 30% Cohen 2000 SLN/ALND 3831 82% 28/30 90% Kinoshita 2006 SLN/ALND 7772/77 93% 3/27 11% 72/77 96% B-27 42889%11%70/125 56%

13. Kuerer, Sahin, et al (1999) 191 pts “cyto +” ALN => neoadj chemo Surgery ALND 43 pts ALND “neg” re-eval confirmed Neg (add’l 1112 sections/half IHC) =>43 of 191 “+” converted to neg (23%) by neoadj chemo Of those 43, 11 were N1 and 32 were N2 If Converted to Neg: 5 yr surv = 87% If Residual Positive: 5 yr surv = 51% If Occult Positive (10%): 5 yr = 75% Proposed: maybe consider SLN

14. Van Rijk, Nieweg, et al 2006 18 studies SLN after neoRX, SLN ID 89%, FN 10% Then studied: SLN in 25 T2 preRX if pre SLN + then ALND after neoadj 10 pos SLN=>post Rx ALND=> 4 pts addl nodes pos in compl ALND 14 SLN Neg pts=> no completion ALND =>no recurrence 18 mo

15. Kahn, Sabel, et al 2005 91 patients pre neo axillary staging Pre neo SLN Bx path Neg 58% (53 pts) Pre neo Pos by US FNA or SLN 42% (38 pts) These 38 pts then Neo=>then ALND 33 of these SLN attempted, found 32 (97%) 33% of these Node Negative on ALND Residual disease 22 patients “False negative” 1 pt (4.5%)

16. SLN before Neo adjuvant Cox,Cox, et al., 2006 89 pts (42 palp or image+ histo proven; 47 cN0) 47 cN0 SLN preRX 82 of 89 + nodes 7 (8%) of 89 neg SLN=>no completion ALND (no recurrence in25 mo) 24 (27%) pCR axilla; 26% grp 1 and 33% grp 2 Demonstrated improved prognosis, avoided ALND 15%, improved staging 53%

17. Comparison Jones, Zabicki, et al., 2005 SLN ID rates better pre than post 100% vs 80.6% Recommend SLN in cN0 pre rx and question its use post neo

18. Propose If accuracy is important then pre treatment workup => stage axilla If clinical + or US+ then Bx; if cN0+US/N0 Then SLN Bx pre treatment If post treatment status important then repeat SLN and complete ALND with addl levels in non SLNs

19. Proposed Neoadjuvant 1) Primary Size ? And/Or 2)“Positive” Nodes ? 3) Inflammatory Axilla cN0 Axilla cN1,2 SLN “Biopsy” Tissue Proof US Biopsy ? Freehand Bx “Positive” Neoadjuvant “Negative” Positive Negative Neoadj “Surgery” Observe axilla “Surgery” SLN and ALND Neoadj “Surgery” With SLN and ALND Axillary Work-up Exam and US

20. Next Question As BCT has increased the number of IBTR patients has increased. Prior axillary procedures have been done What should we do? Does it matter? It should, especially if it is a “new primary” Late vs. early and/or separate site IBTR

21. IBTR ? SLN redo Anticipated ~1-2 % per year BCT patients with IBTR Patients with prior SLN no ALND Patients with prior ALND Need a plan for management ? Importance of node eval for planning Rx

22. Dinan, Nagle, et al 2005 16 pts second IBTR Lymphoscintigraphy pos 69% Ipsi ax, contra ax, supraclav (ipsi and contra)

23. Intra, Trifiro, et al, 2005 79 pts recurrent disease prior SLN - 18 pts cN0 ~ 26 mo after initial Dx/Rx Pre op ID SLN 100% with lymphoscintigrapy and SLN removed average 1.3 SLN pos in 2 patients At 12 mo no recurrences in pts SLN Neg w/o ALND

24. Re-operative SLN Taback, Nguyen, et al 2006 15 pts prior Rx BCT with IBTR and prior SLN or ALND Preop Lymphoscintig + 11 (73%) 3 contralat ax, 5 ipsilat ax, 2 IM, 2 SC, 2 Intra pect Intraop ID 11 of 14, Mets in 3; 2 contralat ax and 1 ipsilat ax

25. Milardovic 2006 Epigastric node Jackson 2006 IBTR prior neg now Pos SLN single pt Agarwal 2005 Two pts prior BCT with ALND => IBTR => SLN contralateral +. SLN neg X 2

26. Newman 2006 14 LRR (10 previous ALND, 2 SLN, 2 no ax surg) SLN ID 90% no mets, non ipsilat drainage in 65%

27. IBTR/ “SLN” StudyPtsSLN IDSitesMets Dinan1670%Ip,con, ax, scl none Intra18100%2+ Taback1573%3conax 5ipsiax 2IM,2S C,2IP 2 con ax 1 ips ax Newman1490%Con axnone Agarwal2100%Con axnone

28. Proposed With IBTR and prior Ax RX SLN ID is possible ~ 70% of the time. The potential sites are many and appearance of uptake is delayed. Imaging needs to be inclusive of “risk” areas and allow extended time, (24 hours ?). Lymphoscintigraphy and planning SLN Bx are justified if a change in therapy would occur (? e.g., if postive contralateral Ax then ALND, or if Increase/change in chemo Rx or Rad Rx.