1. The Treatment of the Axilla in the North of England Cancer Network. Henry Cain ST7 North Tyneside.

2. Current national and local guidelines. Results of NECN axillary surgery audit. Application of results in view of published evidence (Z0011 and beyond)

3. National Guidelines regarding the staging of the Axilla. UK- ABS Guidelines 2009 “All patients diagnosed with invasive breast cancer undergoing surgical treatment should have a pre- operative axillary ultrasound scan, and if appropriate FNA or core biopsy should be carried out.” “If a positive non-operative diagnosis of axillary nodal metastasis is made in a patient undergoing surgery for breast cancer, the patient should normally proceed to an axillary clearance” “Sentinel node biopsy using the combined blue dye/radioisotope technique is a recommended axillary staging procedure for the majority of patients with early invasive breast cancer” “When axillary node clearance is carried out, the level of anatomical dissection should be specified, and at least 10 nodes should be retrieved” “Axillary recurrence should be minimised by effective staging and treatment where appropriate Minimum standard <5% axillary recurrence at 5 years Target <3% axillary recurrence at 5 years”

4. Local Guidelines regarding the staging of the Axilla. NECN Breast Cancer Guidelines 2011 “SLNB is the standard of care for staging the axilla.” “Pre-operative Axillary USS give additional pre-operative staging information” “Patients with proven Histologically malignant lymph nodes are not suitable for SLNB”

5. Current National Guidelines for the treatment of the positive axilla. UK- ABS Guidelines 2009 ‘if the SLN is positive (macro/micro-metastasis), further axillary treatment (cALND or RT) as well as adjuvant systemic therapy is recommended UK- NICE Guidelines 2009 ‘cALND is preferred - gives additional staging information’ USA- ASCO Guidelines 2005 Panel recommends cALND for macro/micro-metastases regardless of the method of detection.

6. Local Guidelines regarding the treatment of the positive axilla. NECN Breast Cancer Guidelines 2011 “Further treatment should be offered to patients with a pre-operative diagnosis of metastatic cancer in the axillary nodes or who have micro or macro mets in the SLNB.” “ The preferred technique is ALND because it gives additional staging information. When further surgery is deemed inappropriate the radiotherapy may be considered”

7. North of England Cancer Network Prospective Audit of Sentinel Lymph Node Biopsy and Axillary Clearance for Breast Cancer Audit compliance with local and national guidelines of pre- operative axillary staging, sentinel lymph node identification, and axillary treatment following identification of a positive SLNB Audit adequacy of ALNC Investigate the role of SLNB for large breast cancers Investigate the value of ALNC following identification of axillary lymph node micro-metastasis Asses the value of intra-operative sentinel lymph node analysis

8. Results of the NCN Axillary surgery Audit. 480 patients included. Data from Northumbria, North Tees and Hartlepool, James Cook and Friarage, Cumbria, Sunderland and RVI. Age range 20-91 (mean 61) 64% symptomatic, 36% screening.

9. Results. Tumour details where available. Tumour TypeNot recorded19 (4%) DCIS38 (8%) Invasive Ductal350 (73%) Invasive none ductal73 (15%) Tumour Size0-19 mm221 (47%) 20-50mm205 (44%) >50mm43 (9%) Tumour Grade162 (14%) 2216 (49%) 3165 (37%) LVIYes106 (24%) No349 (76%)

10. Pre-op Staging. 450 recorded. 445 pre-op USS. 5 no staging. 7 additional MRI information. 1 additional CT information.

11. Results of Pre-op Staging Staging results. N=445 USS normal323 USS abnormal n=122 FNA75 Core Bx43 Both4 Pathological Sample Negative.59 Positive.63 (51%) 361 patients proceeded to SLNB following negative staging. 58 patients underwent ANC due to positive pre-op staging.

12. Sentinel Node Biopsy Technique. 400 recorded 277 (69%) dual technique. 33 blue dye only. 90 radio-isotope only. 2 documented as failed > ANS/Clearence. 1- 15 sentinel nodes taken (mode 1) None sentinel (or sample) nodes taken in addition to sentinel node in 42 cases.

13. Results of SLNB Results AvailableN=398 (401) SLNBNegative307 (77%) Positive91 (23%) Pathology of pos (n91)ITC4 (4.4%) Micro26 (28.6%) Macro61 (67%) No cases reported of negative sentinel nodes but tumour found in non-sentinel node sample.

14. Treatment of positive SLNB SLNB resultNo treatmentANCDXTANC&DXT Positive (91)13 (14%)57 (63%)20 (22%)1 (1%) ITC (4)31 Micro met (26)5 (19%)16 (61%)4 (15)1 (4%) Macro met (61)4 (7%)40 (66%)17 (28%)0

15. Axillary Lymph Node Clearance. ANC resultsN=125 IndicationPos pre-op58 (46%) Pos SLNB50 (40%) Pos intra op ass4 (3%) Other13 ( 11%) Nodes RemovedMode13 < 10 nodes26 (20%)

16. Results of ANC for positive SLNB SLNB resultANC negativeANC Positive Positive (n50)39 (78%)11 (22%) ITC (n1)01 (100%!!) (3/5) Micro (n15)12 (80%)3 (20%) Macro (n34)27 (79%)7 (21%) 8/11 had 3 or less further nodes. 2 had 4 further positive nodes. 1 had 5 further positive nodes. Micro mets 2= 1 node, 1 = 2 nodes. No significant predictive value for tumour type, size, grade or LVI.

17. Intra-operative Assessment. Intra op ass (n=91) SLNB negative SLNB postive MicroMacro Negative75 (87%)12 (13%)39 Positive04 (100%)13 Of the 12 false negatives 9 went on to have ANC following positive SLNB Of the 4 positive intra op assessment all went on to have ANC. Of these 2 were negative 1 had 1 micro met in 20 nodes 1 had 5/13 macro mets. Sensitivity 25%, Specificity 100%, PPV 100%, NPV 86%

18. Results of pre op staging. 22% cases false negative pre op staging overall but 15% for macro mets alone. Sensitivity 39%, Specificity 98% PPV=90% NPV 78% 52/112 cases of positive axilla were identified by pre-op staging (46%) Pre op ass (n=419) SLNB or ANC negativ e SLNB or ANC positive ITCMicroMacro Negativ e (n361) 28180 (22%) 32255 (15%) Positive (n=58) 6(10%)52

19. Results of negative pre op staging. SLNB negativeSLNB positiveP value Overall30791 Tumour typeDuctal19464 Special type50120.4 Tumour grade14770.055 212349 38624 Tumour Size0-19mm15127 (15%)0.004* 20-50mm10345 > 50mm217 LVINo24343 Yes2433 (58%) <0.0001* Pre op FNA/BxNo23872 Yes4380.3

20. SLNB in T3 tumours 28/43 underwent SLNB 8/28 (29%) positive 6 went on to ANC 12/43 positive pre op staging went on to ANC. 20 ANC 14 (70%) positive

21. Summary Excellent rate of pre-op staging with adequate effectiveness. SLNB applied in majority of cases. 23% of SLNB positive. 20% of ANC for micro mets had further disease. 21% of ANC for macro mets had further disease.

22. North of England Cancer Network Prospective Audit of Sentinel Lymph Node Biopsy and Axillary Clearance for Breast Cancer Audit compliance with local and national guidelines of pre- operative axillary staging, sentinel lymph node identification, and axillary treatment following identification of a positive SLNB Audit adequacy of ALNC Investigate the role of SLNB for large breast cancers Investigate the value of ALNC following identification of axillary lymph node micro-metastasis Asses the value of intra-operative sentinel lymph node analysis

23. Axillary conservation We accept local recurrence rates of 5-10% over 10 years following breast conservation and RT So why do we agonise over axillary recurrence rates of 1-2% over 5 years after SLNB Especially as the evidence that axillary recurrence rates translate to survival differences is hard to come by? Yet the morbidity of ALND is all too clear

24. Case for ANC. cALND is therapeutic – SLNB is a staging test only so require cALND to eradicate any residual axillary disease – Improves local disease control – Improves survival cALND gives additional useful prognostic information – Total nodal disease burden – This information helps refine adjuvant treatment

25. Case against ANC Majority do not have further nodal disease – Minimal additional prognostic information – Now have better biological prognostic markers Residual axillary disease does not translate into local recurrence – Evidence that ALND has survival gain in any BC patient is limited cALND represents overtreatment with substantial morbidity

26. Is there a group of patients that following a positive SLNB be spared and ANC? Relevant Studies. Z0011. Application to these Audit results.

27. RCT into Treatment of positive SLNB ACOSOG Z0011 – Local recurrence, OS and DFS is equivalent for low burden (micro and macro), H&E detected SLN disease, with or without cALND after median FU 6yrs Guiliano et al Annals of Surgery 2010 252(3) 426-433 Guiliano et al JAMA 2011 305 (6) 569-606 IBCSG Trial 23-01 SABCS 2011 – Local recurrence, OS and DFS is equivalent for VERY low burden (micro and ITC), IHC or F/S detected disease with or without ALND after median FU 5 years

28. Z0011 Randomised trial to establish role of cALND in SLN positive patients 1999-2004 SLN +ve (H&E) randomised to cALND or not. – All T1/T2 ( <5cm): BCT +RT – Adjuvant therapy not controlled (at discretion) – Compared OS,DFS, loco-regional control

29. Z11: Results Median follow up 6.2yrsSLNB alone SLNB+ ALND P value N446445 Demographics, tumour characteristics, systemic treatment similar n/s Median nodal yield217 Recurrence 5yrs Breast Axilla 2.7 2.1% 0.6% 5.1 3.7% 1.3% n/s 0S 5 yrs DFS 5yrs 92.5% 83.8% 91.9% 82.2% n/s *NB. ALND arm ~27% had additional positive nodes

30. Application Z0011 to our results. Difficult due to limitations in audit regarding surgery type and adjuvant DXT but... Similar pos ANC following pos SLNB. Flaws with Z0011 but best we have at the moment. Future trials awaited AMAROS & POSNOC?? Can pts afford for us to wait?

31. Thank you.