Sentinel Lymph Node in Breast Cancer: Review Article from a Pathologist’s Point of View

다국어 초록 (Multilingual Abstract)

Breast cancer staging, in particular N-stage changed most significantly due to the advanced technique of sentinel lymph node biopsy two decades ago. Pathologists have more thoroughly examined and scrutinized sentinel lymph node and found increased number of small volume metastases. While pathologists use the strict criteria from the Tumor Lymph Node Metastasis (TNM) Classification, studies have shown poor reproducibility in the application of American Joint Committee on Cancer and International Union Against Cancer/TNM guidelines for sentinel lymph node classification in breast cancer. In this review article, a brief history of TNM with a focus on N-stage is described, followed by innate problems with the guidelines, and why pathologists may have difficulties in assessing lymph node metastases uniformly. Finally, clinical significance of isolated tumor cells, micrometastasis, and macrometastasis is described by reviewing historical retrospective data and significant prospective clinical trials.

참고문헌 (Reference)

1 Cserni G, "Variations in sentinel node isolated tumour cells/micrometastasis and non-sentinel node involvement rates according to different interpretations of the TNM definitions" 44 : 2185-2191, 2008

2 Denoix PF, "Tumor, node and metastasis (TNM)" 1 : 1-69, 1944

3 Yi M, "Trends in and outcomes from sentinel lymph node biopsy (SLNB) alone vs. SLNB with axillary lymph node dissection for node-positive breast cancer patients: experience from the SEER database" 17 (17): 343-351, 2010

4 Hansen NM, "The time has come to change the algorithm for the surgical management of early breast cancer" 137 : 1131-1135, 2002

5 Chen SL, "The prognostic significance of micrometastases in breast cancer: a SEER population-based analysis" 14 : 3378-3384, 2007

6 AMAROS, "The EORTC 10981-22023 AMAROS trial" AMAROS

7 Sobin LH, "TNM classification of malignant tumours" John Wiley and Sons Inc 2009

8 Lucci A, "Surgical complications associated with sentinel lymph node dissection (SLND) plus axillary lymph node dissection compared with SLND alone in the American College of Surgeons Oncology Group Trial Z0011" 25 : 3657-3663, 2007

9 Singletary SE, "Staging system for breast cancer: revisions for the 6th edition of the AJCC Cancer Staging Manual" 83 : 803-819, 2003

10 Huvos AG, "Significance of axillary macrometastases and micrometastases in mammary cancer" 173 : 44-46, 1971

11 Gill G, "Sentinel-lymphnode-based management or routine axillary clearance? One-year outcomes of sentinel node biopsy versus axillary clearance (SNAC):a randomized controlled surgical trial" 16 : 266-275, 2009

12 Krag DN, "Sentinel-lymph-node resection compared with conventional axillary-lymph-node dissection in clinically node-negative patients with breast cancer: overall survival findings from the NSABP B-32 randomised phase 3 trial" 11 : 927-933, 2010

13 Cote RJ, "Role of immunohistochemical detection of lymph-node metastases in management of breast cancer" 354 : 896-900, 1999

14 Straver ME, "Role of axillary clearance after a tumor-positive sentinel node in the administration of adjuvant therapy in early breast cancer" 28 : 731-737, 2010

15 Vestjens JH, "Relevant impact of central pathology review on nodal classification in individual breast cancer patients" 23 : 2561-2566, 2012

16 Vergara-Lluri ME, "Recurrence rates in breast cancer patients who had sentinel lymph node biopsy alone versus completion axillary lymph node dissection: a 7-year clinical follow-up study" 20 : 666-668, 2014

17 Mansel RE, "Randomized multicenter trial of sentinel node biopsy versus standard axillary treatment in operable breast cancer: the ALMANAC Trial" 98 : 599-609, 2006

18 Clare SE, "Prognostic significance of occult lymph node metastases in node-negative breast cancer" 4 : 447-451, 1997

19 Sedmak DD, "Prognostic significance of cytokeratin-positive breast cancer metastases" 2 : 516-520, 1989

20 de Mascarel I, "Prognostic significance of breast cancer axillary lymph node micrometastases assessed by two special techniques: reevaluation with longer followup" 66 : 523-527, 1992

21 Tvedskov TF, "Prognostic significance of axillary dissection in breast cancer patients with micrometastases or isolated tumor cells in sentinel nodes: a nationwide study" 153 : 599-606, 2015

22 Fitzgibbons PL, "Prognostic factors in breast cancer. College of American Pathologists Consensus Statement 1999" 124 : 966-978, 2000

23 Fisher ER, "Pathologic findings from the National Surgical Adjuvant Breast Project (Protocol No. 4). V. Significance of axillary nodal micro- and macrometastases" 42 : 2032-2038, 1978

24 Chen ZL, "Occult metastases in the axillary lymph nodes of patients with breast cancer node negative by clinical and histologic examination and conventional histology" 9 : 239-248, 1991

25 Nasser IA, "Occult axillary lymph node metastases in “node-negative”breast carcinoma" 24 : 950-957, 1993

26 van Deurzen CH, "Non-sentinel lymph node metastases associated with isolated breast cancer cells in the sentinel node" 100 : 1574-1580, 2008

27 Turner RR, "Nodal stage classification for breast carcinoma: improving interobserver reproducibility through standardized histologic criteria and image-based training" 26 : 258-263, 2008

28 Trojani M, "Micrometastases to axillary lymph nodes from carcinoma of breast: detection by immunohistochemistry and prognostic significance" 55 : 303-306, 1987

29 de Boer M, "Micrometastases or isolated tumor cells and the outcome of breast cancer" 361 : 653-663, 2009

30 Weaver DL, "Metastasis detection in sentinel lymph nodes: comparison of a limited widely spaced (NSABP protocol B-32) and a comprehensive narrowly spaced paraffin block sectioning strategy" 33 : 1583-1589, 2009

31 Cserni G, "Meta-analysis of non-sentinel node metastases associated with micrometastatic sentinel nodes in breast cancer" 91 : 1245-1252, 2004

32 Giuliano AE, "Lymphatic mapping and sentinel lymphadenectomy for breast cancer" 220 : 391-398, 1994

33 Kim T, "Lymphatic mapping and sentinel lymph node biopsy in early-stage breast carcinoma: a metaanalysis" 106 : 4-16, 2006

34 Fu Y, "Is axillary lymph node dissection necessary after sentinel lymph node biopsy in patients with mastectomy and pathological N1 breast cancer?" 21 : 4109-4123, 2014

35 McCready DR, "Influence of the new AJCC breast cancer staging system on sentinel lymph node positivity and false-negative rates" 96 : 873-875, 2004

36 Cserni G, "Improving the reproducibility of diagnosing micrometastases and isolated tumor cells" 103 : 358-367, 2005

37 Hansen NM, "Impact of micrometastases in the sentinel node of patients with invasive breast cancer" 27 : 4679-4684, 2009

38 Pugliese MS, "Impact and outcomes of routine microstaging of sentinel lymph nodes in breast cancer: significance of the pN0(i+) and pN1mi categories" 16 : 113-120, 2009

39 Viale G, "Histologic detection and clinical implications of micrometastases in axillary sentinel lymph nodes for patients with breast carcinoma" 92 : 1378-1384, 2001

40 Weaver DL, "Effect of occult metastases on survival in node-negative breast cancer" 364 : 412-421, 2011

41 Cserni G, "Distinction of isolated tumour cells and micrometastasis in lymph nodes of breast cancer patients according to the new Tumour Node Metastasis (TNM)definitions" 47 : 887-894, 2011

42 de Mascarel I, "Distinction between isolated tumor cells and micrometastases in breast cancer: is it reliable and useful?" 112 : 1672-1678, 2008

43 Cyr A, "Disease recurrence in sentinel node-positive breast cancer patients forgoing axillary lymph node dissection" 19 : 3185-3191, 2012

44 Cserni G, "Discriminating between micrometastases and isolated tumor cells in a regional and institutional setting" 15 : 347-354, 2006

45 Hainsworth PJ, "Detection and significance of occult metastases in node-negative breast cancer" 80 : 459-463, 1993

46 Bilimoria KY, "Comparison of sentinel lymph node biopsy alone and completion axillary lymph node dissection for node-positive breast cancer" 27 : 2946-2953, 2009

47 Connolly JL, "Changes and problematic areas in interpretation of the AJCC Cancer Staging Manual, 6th Edition, for breast cancer" 130 : 287-291, 2006

48 Singletary SE, "Breast cancer staging: working with the sixth edition of the AJCC Cancer Staging Manual" 56 : 37-47, 2006

49 Bleiweiss IJ, "Axillary sentinel lymph nodes can be falsely positive due to iatrogenic displacement and transport of benign epithelial cells in patients with breast carcinoma" 24 : 2013-2018, 2006

50 Giuliano AE, "Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial" 305 : 569-575, 2011

51 Hieken TJ, "Axillary dissection versus no axillary dissection in patients with sentinel-node micrometastases: commentary on the IBCSG 23-01 Trial" 2 : 128-132, 2013

52 Galimberti V, "Axillary dissection versus no axillary dissection in patients with sentinel-node micrometastases (IBCSG 23-01): a phase 3 randomised controlled trial" 14 : 297-305, 2013

53 Guenther JM, "Axillary dissection is not required for all patients with breast cancer and positive sen tinel nodes" 138 : 52-56, 2003

54 Lyman GH, "American Society of Clinical Oncology guideline recommendations for sentinel lymph node biopsy in early-stage breast cancer" 23 : 7703-7720, 2005

55 Apple SK, "Accurate classification of sentinel lymph node metastases in patients with lobular breast carcinoma" 19 : 360-364, 2010

56 Fleming ID, "AJCC cancer staging manual" Lippincott-Raven 1997

57 Edge SB, "AJCC cancer staging manual" Springer 2009

58 Greene FL, "AJCC cancer staging manual" Springer-Verlag 2002