Sentinel Lymph Node Biopsy in Breast Cancer

1. Sentinel Lymph Node Biopsy in Breast Cancer Dr Peter Lovrics St Joseph�s Healthcare, Department of Surgery, McMaster University Hamilton, Ontario

2. Axillary Dissection Breast cancer is a common disease. Level I & II axillary dissection has been the standard of care .

3. Why not do ALND? Inaccurate predictor of prognosis. Primary tumour & patient characteristics guide adjuvant therapies. Radiation therapy & delayed ALND provide effective local control. No impact on survival. Morbidity

5. Why perform ALND? Staging ? prognosis Staging ? guide chemo & radiation therapy Longterm regional control Minimal morbidity Positive impact on survival?

6. Is there a better way? Acceptance of BCS & minimizing surgical morbidity. Increased awareness & widespread adoption of screening ? decreased size of primary & earlier stage. Enhanced, more accurate pathological examination of nodal tissue. Noninvasive modalities

7. Lymphatic Mapping Drainage primarily to the axilla. Isolated internal mammary or supraclavicular drainage rare. Morton ? melanoma Cabanas ? penile carcinoma

9. Sentinel lymph node The lymphatic effluent of a tumour drains preferentially to one (or more) �sentinel� lymph node(s). The sentinel node accurately reflects the disease status of the entire nodal basin. Offers opportunity for enhanced pathological evaluation.

10. SLN localization Radiopharmaceutical injection ? uptake into lymphatics ? phagocytosis & retention by lymph node. Minimal diffusion/absorption. Depends on particle size. Detectable by gamma camera (lymphoscintogram) & by handheld gamma probe.

11. SLN localization Vital blue dye injection ? uptake into lymphatics ? retention by lymph nodes. Significant diffusion, absorption & passage. Rapid Visible Complementary to radiopharmaceutical

12. Identification of the Sentinel Node

13. Intraop Identification of Sentinel Node (s)

15. Blue Dye Allergic reactions Inform anaesthesia � drop in saturation monitor Patient may appear �ashen�, cadaveric ? inform recovery room nurses Counsel patient re blue-green urine/BM Skin Tatooing

16. Validation of SLN hypothesis Does SLN reflect disease status of the nodal basin? Can SLN be consistently identified? What is the risk of a false negative SLNB? Can SLNB technique be widely disseminated with acceptable success & accuracy?

17. Validation of SLN hypothesis Giuliano et al, Ann Surg 1999 Negative SLN ? positive ALN: 1/1087 Veronesi et al, Lancet 1997: Negative SLN ? positive ALN: 3% Krag et al, NEJM 1998: Negative SLN ? positive ALN: 3% Risk of false negative ALND: 3-10%

18. Validation of SLN concept Cox et al, J Am Coll Surg 1997: 96% successful identification of SLN Giuliano et al, J Clin Onc 1997: 99% successful identification of SLN Veronesi et al Lancet 1997: 98% successful identification of SLN

19. Implementation & dissemination Krag & Giuliano: identified �learning curve� in both identification rate & false negative rate. However, validation series, multicentered trials & meta-analyses have demonstrated that technique can be implemented with acceptable accuracy rates.

20. Learning Curves Data suggest increased volume lead to decreased failure rates COX learning curve- logistic regression on mapping failures <3 SLN biopsies/month � 86% success rate 3-6 SLN biopsies/month- 89 % success rate >6 SLN/biopsies/month- 97% success rate

21. Learning Curve & FN Rate Four multicenter trials: Decrease in False Negative rate to =or < 5% after 20-30 procedures A minimum of 25 cases with completion ALND is recommended

22. Is SLNB better than ALND? Enhanced staging: single/small number of nodes enables serial sectioning with H & E, and also immunohistochemical staining (IHC). Most series: nodal positivity rates 10-25% higher than ALND. Reflects historical rates of serial sectioning entire ALND.

23. Pathology

24. Micrometastasis

25. Revised AJCC Staging pN0 pN0 (i-)-negative IHC pN0 (i+) positive IHC but no cluster > 0.2 mm (Isolated Tumour Cells) pN1mi: micrometastases (greater than 0.2 and none greater than 2.0 mm) pN1: 1-3 positive nodes

26. Is SLNB better than ALND? Morbidity: ALND is the leading cause of decreased cancer-specific quality of life. Postoperative complications Lymphedema: 3-10% Numbness: 30-60% Chronic pain/neuritis: 20-30%

27. Is SLNB better than ALND? Burak et al Am J Surg 2002 & Temple et al Ann Surg Onc 2002: Significantly less lymphedema, numbness & pain. Veronesi et al NEJM 2004: significantly fewer patients with edema, pain, numbness, & improved mobility & cosmesis

28. ACOSOG Z010 5237 patients Surgical outcomes at 30 days and 6 months Anaphylaxis 0.1% Wound infection 1.0% Seroma 7.1% Hematoma 1.4% Axillary parasthesias 8.6% Lymphedema 6.9%

29. Unresolved issues Patient selection Implementation & accreditation. Importance of micrometastatic disease. Technical controversies & variations. Intraoperative SLN evaluation. Internal mammary nodes What to do with a positive SLN?

30. Clinical trials NSABP B-32: studies node negatives Survival, regional control & toxicity of SLNB versus ALND. Prognostic value of IHC. Technical success rate. Target accrual: 5400 patients

31. NSABP- B-32

32. Clinical trials: ACOSOG Z0010: all patients SLNB ? risk of negative SLNB & no further surgery with or without positive micrometastatic disease. Target accrual: 5300 Z0011: all patients SLNB ? risk of positive SLNB and full ALND versus no ALND (with breast XRT & adjuvant therapy). Target accrual: 1900

33. Integration of Sentinel NodeCanadian Survey Results Canadian Survey 61% response rate 1413 surgeons- 490 treated breast cancer Doubling of # of surgeons performing SLN over five year period

34. 2006 Survey Results 76% learned SLN procedure from mentor or Formal course 56% cited inadequate resources as a deterrent Specifically lack of gamma probe or nuclear medicine resources

35. Is Sentinel Node Biopsy the Standard of Care? Veronesi- RCT N Engl J Med. 2003 Aug 7;349(6):546-53. Underpowered ( n=516) Short follow-up Definitive trial-----NSABP 32 Trial 23-01----European IO, Italy ALMANAC Trial- Quality

36. National Surgeons Survey

37. Canadian Survey 2006

38. What to do with a positive SLN? In patients with a SLN routine H&E: 30-40% disease on completion ALND ? ALND If micrometastatic disease: 10-35% ? If ITC: <10% risk of additional +ve nodes ? Literature difficult to interpret. NSABP/ACOSOG studies

39. Nomogram for Predicting additional Axillary Metasases Memorial Sloan Kettering Cancer Center Primary characteristics: size, grade, LVI, ER, multifocality SLN: number positive & negative, detection method. Calculates risk of further positive nodes in completion axillary dissection. Van Zee et al. Ann Surg Oncol:1140-1151, 2003

40. Sentinel lymph node biopsy It�s here. More accurate & less morbid. Accepted as standard of care. Unresolved issues: variances in techniques, implementation/standards, positive SLN & patient selection.