1. S ENTINEL L YMPH N ODE M ICROMETASTASIS IN B REAST C ANCER Anthony Fong Yan Chai Hospital

2. S ENTINEL L YMPH N ODE First node encountered by tumor cell Will spread first to lymph nodes close to the tumor before it spreads to other parts of the body If the sentinel lymph node does not contain cancer, then there is a high likelihood that the cancer has not spread to any other area of the body Veronesi U, Luini A, Galimberti V, Marchini S, Sacchini V, Rilke F. Eur J Surg Oncol. 1990 Apr;16(2):127-33. Extent of metastatic axillary involvement in 1446 cases of breast cancer.

3. S ENTINEL L YMPH NODE False negative value 8.8% Negative predictive value 95.4% http://www.mayoclinic.org/breast-cancer

4. L OCALIZATION OF SENTINEL L YMPH NODE Isosulfan blue dye Technetium-99 sulfur colloid False negative rate : 5.8% http://www.cancernetwork.com McMasters KM, Tuttle TM, Carlson DJ et al Sentinel lymph node biopsy for breast cancer: a suitable alternative to routine axillary dissection in multi-institutional practice when optimal technique is used. J Clin Oncol. 2000 Jul;18(13):2560-6.

5. P ATHOLOGICAL EXAMINATION OF SLN H & E staining Immunohistochemistry Molecular techniques Klevesath MB, Bobrow LG, Pinder SE, Purushotham AD. The value of immunohistochemistry in sentinel lymph node histopathology in breast cancer. Br J Cancer. 2005 Jun 20;92(12):2201-5.

6. MICROMETASTASIS & ISOLATED TUMOR CELLS

7. 7 TH AJCC 7 th AJCC

8. P ATHOLOGICAL STAGING OF LYMPH NODE Pathologic pN pNXRegional lymph nodes cannot be assessed (for example, previously removed, or not removed for pathologic study) pN0No regional lymph node metastasis identified histologically. pN0(i−)No regional lymph node metastases histologically, negative IHC pN0(i+)Malignant cells in regional lymph node(s) no greater than 0.2 mm (detected by H&E or IHC including ITC) pN0(mol−)No regional lymph node metastases histologically, negative molecular findings (RT-PCR) pN0(mol+)Positive molecular findings (RT-PCR)**, but no regional lymph node metastases detected by histology or IHC pN1Micrometastases; or metastases in 1–3 axillary lymph nodes; and/or in internal mammary nodes with metastases detected by sentinel lymph node biopsy but not clinically detected pN1miMicrometastases (greater than 0.2 mm and/or more than 200 cells, but none greater than 2.0 mm)

9. P ATHOLOGICAL STAGING OF LYMPH NODE Pathologic pN pNXRegional lymph nodes cannot be assessed (for example, previously removed, or not removed for pathologic study) pN0No regional lymph node metastasis identified histologically. pN0(i−)No regional lymph node metastases histologically, negative IHC pN0(i+)Malignant cells in regional lymph node(s) no greater than 0.2 mm (detected by H&E or IHC including ITC) pN0(mol−)No regional lymph node metastases histologically, negative molecular findings (RT-PCR) pN0(mol+)Positive molecular findings (RT-PCR), but no regional lymph node metastases detected by histology or IHC pN1Micrometastases; or metastases in 1–3 axillary lymph nodes; and/or in internal mammary nodes with metastases detected by sentinel lymph node biopsy but not clinically detected pN1miMicrometastases (greater than 0.2 mm and/or more than 200 cells, but none greater than 2.0 mm)

11. ASCO G UIDELINE Recommends routine ALND for patients with a positive SNB on the basis of routine histopathologic examination. It remains unclear whether isolated tumor cells (pN0) detected with hematoxylin and eosin staining or special stains represent an adverse prognostic indicator. Metastasis is found in nonsentinel nodes in about 10% of patients with isolated tumor cells in the SLN and in 20% to 35% of patients with micrometastasis in the SLN.

12. ASCO G UIDELINE Until further studies addressing the clinical relevance of isolated tumor cells or micrometastases in the SLN are complete, the Panel recommends routine ALND for patients with micrometastases ( >0.2 mm but < 2.0 mm) found on SNB, regardless of the method of detection.

13. A XILLIARY DISSECTION IN SLN MICROMETASIS

14. AD IN SLN MICROMETASTASIS

15. A XILLARY R ECURRENCE R ATE IN B REAST C ANCER P ATIENTS WITH N EGATIVE S ENTINEL L YMPH N ODE B IOPSY OR C ONTAINING M ICROMETASTASES AND W ITHOUT F URTHER L YMPHADENECTOMY : A MONOCENTRIC R EVIEW OF 8 Y EARS AND 481 C ASES Negative SLNB no additional CALND (n=481) Axillary relapse in only 1 patient (0.2%) SLNB contained micrometastases and no further CALND (n=45) No axillary relapse in this group Mean FU time 48 months

17. AVOIDING AXILLARY TREATMENT IN SENTINEL LYMPH NODE MICROMETASTASES OF BREAST CANCER : A PROSPECTIVE ANALYSIS OF AXILLARY OR DISTANT RECURRENCE Patient with early breast cancer (tumor <3cm) with favorable characteristics 1178 patient with SLN 59 (5%) had micrometastases 14 (24%) underwent ALND After median 60month, no patient in SLN MM group without ALND developed axillary recurrence

18. SLN MM AFFECTING PROGNOSIS

19. P ROGNOSIS

20. M ICROMETASTASES OR I SOLATED T UMOR C ELLS AND THE O UTCOME OF B REAST C ANCER Identify women with invasive breast cancer with SLN before 2006 from Netherlands Caner Registry Include patient with favourable primary tumor characteristics Tumors <= 1cm in diameter, irrespective of grade Tumors >1cm to <= 3cm, grade 1 or 2 Node negative disease randomly selected from years 2000 and 2001

21. M ICROMETASTASES OR I SOLATED T UMOR C ELLS AND THE O UTCOME OF B REAST C ANCER Node negative n = 856 ITC / MM with no adjuvant therapy n = 856 ITC / MM with adjuvant therapy n = 995

22. M ICROMETASTASES OR I SOLATED T UMOR C ELLS AND THE O UTCOME OF B REAST C ANCER

23. C ONCLUSION Micro-metastasis in breast cancer indicates a inferior prognosis Axillary dissection may not be necessary in patient with micrometastasis Role of adjuvant therapy

24. END