Sentinel Lymph Node Biopsy Breast Cancer

1. Sentinel Lymph Node BiopsyBreast Cancer Dr. LAI, Eric C.H. Department of Surgery North District Hospital

2. Sentinel Lymph Node BiopsyIntroduction & Background • Background information of Axillary lymph node dissection • Development of Sentinel lymph node biopsy

3. Sentinel Lymph Node BiopsyIntroduction & Background Axillary Lymph Node Dissection

4. Sentinel Lymph Node BiopsyIntroduction & Background • Axillary lymph node dissection (ALND) – an integral part of breast cancer management since Halsted introduced radical mastectomy in the mid-1800s • After World War II, Waangensteen and others advocated removing the supraclavicular and internal mammary lymph nodes and the axillary nodes • Nowadays, ALND is a gold standard for assessment of lymph node status. • Recently, some have suggested that removing clinically normal axillary nodes is not therapeutic, and so is unnecessary

5. Sentinel Lymph Node BiopsyIntroduction & Background • Role of Axillary lymph node dissection (ALND) • Accurate staging & prognostic information • Selection for adjuvant systemic therapy • Impact on survival (Controversial)

6. Sentinel Lymph Node BiopsyIntroduction & Background • Axillary recurrence after ALND 0% to 2.1% • Acute complication rate (e.g. fluid collection, infection, pain) 20% to 30% • Chronic complication rate (e.g. lymphoedema) 20% to 30%

7. Sentinel Lymph Node BiopsyIntroduction & Background • In fact, the majority (~ 70%) of women with clinically negative axilla (N0) will prove to be microscopically negative • With improvement in screening and diagnostic investigation, more and more small primary tumour detected. • More breast cancer patients today do not have lymph node metastases.

8. Sentinel Lymph Node BiopsyIntroduction & Background • ALND offers no benefit for this group of patients, and may do harm • An accurate noninvasive techniques for assessment of axillary status is needed.

9. Sentinel Lymph Node BiopsyIntroduction & Background • Clinical assessment 29-38% false negative rate • Radiographic methods(mammography, computed tomography, positron emission tomography) 10-30% false negative rate • Random sampling of axillary nodes 40% false negative rate • Only Level I lymph node dissection 10-15% false negative rate

10. Sentinel Lymph Node BiopsyIntroduction & Background Sentinel Lymph Node Biopsy

11. Sentinel Lymph Node BiopsyIntroduction & Background • Concept of Sentinel Lymph Node Biopsy The first node in the regional nodal basin that drains a primary tumour, reflects the tumour status of the entire nodal basin

12. Sentinel Lymph Node BiopsyIntroduction & Background • Advantage • Accurate assessment of axillary lymph node involvement • Minimal morbidity • Accuracy • Identification rates • False-negative rates

13. Sentinel Lymph Node BiopsyIntroduction & Background • Patients T1,2 primary tumour with N0

14. Sentinel Lymph Node BiopsyIntroduction & Background • Using a radioactive material or a blue dye, and often both • Local injection is into the breast tissue • The material will migrate through the lymphatics of the breast to the first lymph node draining the tumour. • The node(s) are then identified by color or by a handheld gamma probe. • They are removed and examined microscopically for the presence of metastatic tumour cells, often by frozen section examination.

15. Sentinel Lymph Node BiopsyIntroduction & Background • Since the histologic status of the sentinel node is thought to represent the status of the entire axillary node basin, failure to detect metastasis in the sentinel node accurately predicts the negativity of the remaining axillary nodes and mitigates the need for a more extensive axillary dissection.

16. Sentinel Lymph Node BiopsyIntroduction & Background • In 1960, Gould et al. described sentinel lymph node biopsy in parotid carcinoma Gould EA, Winship T, Philbin PH, et al. Cancer 1960;13:77-8 • In 1977, Cabanas introduced the concept of the sentinel node in penile cancer Cabanas RM. Cancer 1977;39:880-882 • In 1992, Morton et al. published a description of the SLND technique for clinical stage I cutaneous melanoma. Morton DL, Wen DR, Wong JH, et al. Arch Surg. 1992;127:392-9 • This technique was further validated by other investigators

17. Sentinel Lymph Node BiopsyIntroduction & Background • In 1994, Giuliano et al. adopted the dye-directed SLND technique in melanoma (a cutaneous tumour system) for use in primary breast cancer (a parenchyma tumour system). Giuliano AE, Kirgan DM, Guenther JM, et al. Ann Surg. 1994;220:391-401 • In 1997, Giuliano et al. refined the technique and patient selection, he had improved the results of SLND. (Identification rate – 93.5%; false negative -0%; accuracy -100%) Giuliano AE, Jones RC, Brennan M, et al. J Clin Oncol. 1997;15:2345-50

18. Sentinel Lymph Node BiopsyContent • Accuracy • Technical aspects • Contraindication • Therapeutic relevance of micrometastases in sentinel lymph nodes • Management of nonsentinel axillary lymph node in women undergoing sentinel lymph node biopsy • Future development

19. Sentinel Lymph Node BiopsyContent Accuracy

20. Sentinel Lymph Node BiopsyAccuracy • SN identification rate and accuracy improved with surgeon experience • The learning curve was around 30 cases • In experienced centre Identification rate – 98 % - 100% False negative rate - <5 % Accuracy – 98 % - 100 %

21. Sentinel Lymph Node BiopsyAccuracy

22. Sentinel Lymph Node BiopsyContent Technical Aspect

23. Sentinel Lymph Node BiopsyTechnical aspects • Injection Method • Injection Agents • Timing of injection • Preoperative lymphosintigraphy

24. Sentinel Lymph Node BiopsyTechnical aspects – Injection Methods • Three Methods • Peritumoural Injection • Dermal or Subdermal Injection • Subareola Injection

25. Sentinel Lymph Node BiopsyTechnical aspect - Peritumoral Injection • Original method used • A logical choice of tracer injection site • The peritumoral lymphatics should connect to the axillary SLN draining that particular region of the breast

26. Sentinel Lymph Node BiopsyTechnical aspect - Peritumoral Injection • Limitations • Difficult for injection in nonpalpable tumour or tumour with large biopsy cavities • Longer learning curve • “Shine through” effect (an intraparenchymal injection of radioactive colloid around in the upper outer quadrant of the breast will obscure an axillary SLN that is close to the injection site)

27. Sentinel Lymph Node BiopsyTechnical aspect – Dermal/Subdermal Injection • The breast parenchyma and overlying skin arise together from embryonic ectoderm, leading to a common lymphatic system and perhaps to a common SLN • A rich lymphatic network is present in the skin of the breast • A higher percentage of tracer injected into the skin reaches the SLN • Identification much easier and more predictable

28. Sentinel Lymph Node BiopsyTechnical aspect – Dermal/Subdermal Injection • Accuracy was confirmed by validation and concordance studies Validation study (axillary LN dissection was performed after sentinel LN biopsy) Concordance studies (one tracer was injected into the dermis, and the other tracer was injected in the peritumoural location) • Accuracy was comparable to those of peritumoral injection

29. Sentinel Lymph Node BiopsyTechnical aspect – Dermal/Subdermal Injection

30. Sentinel Lymph Node BiopsyTechnical aspect – Dermal/Subdermal Injection • Advantage • The SLN is “hotter” and easier to identify • Rapid transit time (SLN biopsy can be performed 30-60 mins. after skin injection compared with several hours after peritumoral injection) 3. Avoid the “shine through” problem

31. Sentinel Lymph Node BiopsyTechnical aspect – Subareola Injection • Lymphatic drainage of the subareolar region mirrors that of the breast parenchyma • Accuracy was confirmed with validation and concordance studies also • Subareolar injection appears to improve SLN identification and to be at least as accurate as peritumoral injection

32. Sentinel Lymph Node BiopsyTechnical aspect – Subareola Injection

33. Sentinel Lymph Node BiopsyTechnical aspect – Subareola Injection • Advantage • Easier to learn & requires less expertise • Can be use in nonpalpable tumour • SN Identification much easier • Rapid transit time from nipple to axilla • Avoid the “shine-through” effect

34. Sentinel Lymph Node BiopsyTechnical aspect – Injection Methods • Peritumoral, dermal or subdermal, and subareolar locations are all potential injection sites • Dermal or subdermal, and subareolar injection technique have distinct advantages and may shorten the learning curve

35. Sentinel Lymph Node BiopsyTechnical aspect – Injection agent • Blue dye Isosulfan blue dye Methylene Blue Patent Blue • Radioactive colloid Technetium-99 sulfur colloid Technetium-99 albumin

36. Sentinel Lymph Node BiopsyTechnical aspect – Single agent versus Double agent Injection • Whether injection of a single agent (Blue dye or radioactive colloid) is as effective as the combination of 2 agents

37. Sentinel Lymph Node BiopsyTechnical aspect – Single agent versus Double agent Injection • McMaster and associates reported a series of 806 patients in 2000. SLN identification rates were similar (single agent, 86%; dual agent, 90%) Single agent use was associated with a significantly higher false negative rate (single agent, 11.8%; dual agent, 5.8%; p<0.05) McMasters KM, Tuttle TM, Carlson DJ, et al. J Clin Oncol. 2000;18:2560-6

38. Sentinel Lymph Node BiopsyTechnical aspect – Single agent versus Double agent Injection • Cody and associates reported that the combination of blue dye and radioactive colloid was complementary for SLN identification in 966 cases (Blue dye alone, 81%; radioactive colloid alone, 87%; both, 95%) Cody HS, Fey J, Akhurst T, et al. Ann Surg Onc 2001;8:13-9

39. Sentinel Lymph Node BiopsyTechnical aspect – Single agent versus Double agent Injection • These data indicate that blue dye and radioactive colloid are complementary and might reduce false negative rate • It is the most common approach currently used in clinical practice

40. Sentinel Lymph Node BiopsyTechnical aspect – Single agent versus Double agent Injection • The dual agent (radioactive colloid plus blue dye) technique is recommended to decrease false negative rates, especially when surgeons are just learning the procedure.

41. Sentinel Lymph Node BiopsyTechnical aspect – Timing of Injection • Blue dye – Nearly all surgeons inject blue dye 5-15 minutes before the procedure • Radioactive colloid injection – The timing varies between surgeons and institutes • At least 30-60 minutes is required for the colloid to localize in the SN

42. Sentinel Lymph Node BiopsyTechnical aspect – Timing of Injection • Several studies have now demonstrated that it is feasible to wait up to 24 hours after injection of the radiocolloid to perform lymphatic mapping • Day before injection provides more flexibility for operation schedule

43. Sentinel Lymph Node BiopsyTechnical aspect – Preoperative Lymphosintigraphy • Many early trials of lymphatic mapping for breast cancer incorporated breast lymphosintigraphy • 2 main reasons for use: • Improve identification rate and false negative rates • Identify extra-axillary SLNs • Most centre do not use now

44. Sentinel Lymph Node BiopsyTechnical aspect – Preoperative Lymphosintigraphy • Rarely identifies axillary SN that cannot be detected with the gamma probe (More sensitive and specific hand held gamma probes became available; the technical details of the procedure were refined) 2. Did not improve SLN identification rate or false negative rate 3. Significantly increase the cost

45. Sentinel Lymph Node BiopsyTechnical aspect – Preoperative Lymphosintigraphy 4. Role of internal mammary lymph node biopsy or dissection is not established • Incidence of isolated internal mammary metastases in the absence of axillary metastases <3%

46. Sentinel Lymph Node BiopsyTechnical aspect – Preoperative Lymphosintigraphy • Dupont and colleagues published the results of internal mammary biopsy in a series of 1470 patients undergoing SLN biopsy for breast cancer in 2001. • Radioactive internal mammary SLNs were identified and removed in 36 patients (2%) • 5/36 (14%) was tumour positive • Only 2/5 had no axillary tumour positive SLNs Dupont EL, Salud CJ, Peltz ES, et al. Am J Surg. 2001;182:321-4.

47. Sentinel Lymph Node BiopsyTechnical aspect – Preoperative Lymphosintigraphy • Most of the internal mammary SLNs can be picked up by hand held gamma probe • Assuming that lymphosintigraphy was performed in all cases, 99.8% preoperative lymphsintigraphy were unnecessary • Breast cancer treatment was not altered based on the study also.

48. Sentinel Lymph Node BiopsyTechnical aspect – Preoperative Lymphosintigraphy • Preoperative lymphosintigraphy is costly and inconvenient • It does not improve results • Removing internal mammary lymph nodes is unlikely to alter treatment or outcomes, and can add unnecessary morbidity

49. Sentinel Lymph Node BiopsyContent Contraindication

50. Sentinel Lymph Node BiopsyContraindication • Palpable lymph nodes • Locally advanced breast cancer • Multifocal breast cancer • Previous breast surgery • Previous radiation to the breast