Sentinel Lymph Node Biopsy in Breast Cancer: Predictors of Axillary and Non-Sentinel Lymph Node Involvement

Öz

Background: Sentinel lymph node biopsy is a standard method for the evaluation of axillary status in patients with T1-2N0M0 breast cancers. Aims: To determine the prognostic significance of primary tumour-related clinico-histopathological factors on axillary and non-sentinel lymph node involvement of patients who underwent sentinel lymph node biopsy. Study design: Retrospective clinical study. Methods: In the present study, 157 sentinel lymph node biopsies were performed in 151 consecutive patients with early stage breast cancer between June 2008 and December 2011. Results: Successful lymphatic mapping was obtained in 157 of 158 procedures (99.4%). The incidence of larger tumour size (2.543±1.21 vs. 1.974±1.04), lymphatic vessel invasion (70.6% vs. 29.4%), blood vessel invasion (84.2% vs. 15.8%), and invasive lobular carcinoma subtype (72.7% vs. 27.3%) were statistically significantly higher in patients with positive SLNs. Logistic stepwise regression analysis disclosed tumour size (odds ratio: 1.51, p=0.0021) and lymphatic vessel invasion (odds ratio: 4.68, p=0.001) as significant primary tumour-related prognostic determinants of SLN metastasis. Conclusion: A close relationship was identified between tumour size and lymphatic vessel invasion of the primary tumour and axillary lymph node involvement. However, the positive predictive value of these two independent variables is low and there is no compelling evidence to recommend their use in routine clinical practice. Turkish Başlık:Meme Kanserinde Bekçi Lenf Nodu Biyopsisi; Aksiller ve Bekçi Dışı Lenf Nodu Tutulumunun Belirleyicileri Anahtar Kelimeler:Meme neoplazmları, lenfatik metastaz, bekçi lenf nodu biyopsisi Arkaplan: Bekçi lenf nodu biopsisi (BLNB), T1-2N0M0 meme kanserli hastalarda aksilla durumunun değerlendirmesi için standart bir yöntemdir. Amaç: BLNB yapılan hastalarda, aksiller ve bekçi dışı lenf nodu tutulumu üzerinde birincil tümör ile ilgili klinik-histopatolojik faktörlerin prognostik önemini belirlemektir. Çalışma Tasarımı: Geriye dönük (retrospektif) klinik çalışma Yöntemler: Bu çalışmada, Haziran 2008 ve Aralık 2011 tarihleri arasında erken evre meme kanseri olan ardışık 151 hastaya 157 BLNB uygulandı. Bulgular: Yüz elli sekiz prosedürün 157'sinde başarılı lenfatik haritalama elde edildi. BLN tutulumu olan hastalarda büyük tümör boyutu (2.543±1.21'e karşı 1.974±1.04), lenf damar invazyonu (LDİ) (%70.6'e karşı %29.4), kan damar invazyonu (KDİ) (%84.2'e karşı %15.8) ve invaziv lobüler karsinom alt tipi (%72.7'e karşı %27.3) istatistiksel olarak anlamlı derecede yüksek bulundu. Lojistik aşamalı regresyon analizinde, birincil tümör ile ilgilibu dört prognostik belirleyicilerden LDİ (Odds Ratio: 4.68, p=0.001) ve tümör boyutu (Odds Ratio: 1.51, p=0.0021) BLN metastazı üzerinde en belirgin etkiye sahipti. Sonuç: Tümör boyutu ve birincil tümörün lenf damar invazyonu ile aksiller lenf nodu tutulumu arasında yakın bir ilişki tespit edilmiştir. Ancak bu iki bağımsız değişkenin pozitif öngörü değeri düşük olup rutin klinik uygulamada kullanımını önermek için hiçbir zorlayıcı kanıt mevcut değildir.

Anahtar Kelimeler

• Breast neoplasms, lymphatic metastasis, sentinel lymph node biopsy.

Sentinel Lymph Node Biopsy in Breast Cancer: Predictors of Axillary and Non-Sentinel Lymph Node Involvement

Öz

Kaynakça

1. Schwartz GF, Giuliano AE, Veronesi U; Consensus Conference Committee. Proceedings of the consensus conference on the role of sentinel lymph node biopsy in carcinoma of the breast, April 19-22, 2001, Philadelphia, Pennsylvania. Cancer 2002;94:2542-51. [CrossRef]
2. Dowlatshahi K, Fan M, Snider H, Habib F. Lymph node micrometastases from breast carcinoma:reviewing dilemma. Cancer 1997;80:1188-97. [CrossRef]
3. Colleoni M, Rotmensz Z, Peruzzotti G, Maisonneuve P, Mazzarol G, Pruneri G, et al. Size of breast cancer metastases in axillary lymph nodes:clinical relevance of minimal lymph node involvement. J Clin Oncol 2005;23:1379-89. [CrossRef] van der Heiden-van der Loo M, Schaapveld M, Ho VK, Siesling S, Rutgers EJ, Peeters PH. Outcomes of a population-based series of early breast cancer patients with micrometastases and isolated tumour cells in axillary lymph nodes. Ann Oncol 2013;24:2794-801. [CrossRef]
4. Grabau D, Jensen MB, Rank F, Blichert-Toft M. Axillary lymph node micrometastasis in invasive breast cancer:national figures on incidence and overall survival. APMIS 2007;115:828-37. [CrossRef]
5. Kuijt GP, Voogd AC, van de Poll-Franse LV, Scheijmans LJ, van Beek MW, Roumen RM. The prognostic significance of axillary lymph-node micrometastases in breast cancer patients. Eur J Surg Oncol 2005;31:500-5. [CrossRef]
6. Wada N, Imoto S. Clinical evidence of breast cancer micrometastases in the era of sentinel node biopsy. Int J Clin Oncol 2008;13:24-32. [CrossRef]
7. Giuliano AE, McCall L, Beitsch P, Whitworth PW, Blumencranz P, Leitch AM, et al. Locoregional recurrence after sentinel lymph node dissection with or without axillary dissection in patients with sentinel lymph node metastases: the American College of Surgeons Oncology Group Z0011 randomized trial. Ann Surg 2010;252:426-33.
8. Aitken E, Osman M. Factors affecting nodal status in invasive breast cancer:a retrospective analysis of 623 patients. Breast J 2010;16:271-8. [CrossRef]

9. Wada N, Imoto S, Yamauchi C, Hasebe T, Ochiai A. Predictors of tumour involvement in remaining axillary lymph nodes of breast cancer patients with positive sentinel lymph node. Eur J Surg Oncol 2006;32:29-33. [CrossRef]
10. Alran S, De Rycke Y, Fourchotte V, Charitansky H, Laki F, Falcou MC, et al. Institut Curie Breast Cancer Study Group, Validation and limitations of use of a breast cancer nomogram predicting the likelihood of non-sentinel node involvement after positive sentinel node biopsy. Ann Surg Oncol 2007;14:2195-201. [CrossRef]
11. Moghaddam Y, Falzon M, Fulford L, Williams NR, Keshtgar MR. Comparison of three mathematical models for predicting the risk of additional axillary nodal metastases after positive sentinel lymph node biopsy in early breast cancer. Br J Surg 2010;97:1646-52. [CrossRef]
12. Gur AS, Unal B, Ozbek U, Ozmen V, Aydogan F, Gokgoz S, et al. Turkish Federation of Breast Disease Associations Protocol MF0801 investigators. Validation of breast cancer nomograms for predicting the non-sentinel lymph node metastases after a positive sentinel lymph node biopsy in a multi-center study. Eur J Surg Oncol 2010;36:30-5. [CrossRef]
13. Zhu L, Jin L, Li S, Chen K, Jia W, Shan Q, et al. Which nomogram is best for predicting non-sentinel lymph node metastasis in breast cancer patients? A meta-analysis. Breast Cancer Res Treat 2013;137:783-95. [CrossRef]
14. Ozmen V, Karanlık H, Cabioglu N, Igci A, Kecer M, Asoğlu A, et al. Factors predicting the sentinel and non-sentinel lymph node metastases in breast cancer. Breast Cancer Res Treat 2006;95:1-6. [CrossRef]
15. Rivadeneira DE, Simmons RM, Christos PJ, Hanna K, Daly JM, Osborne MP. Predictive factors associated with axillary lymph node metastases in T1a and T1b breast carcinomas: analysis in more than 900 patients. J Am Coll Surg 2000;191:1-8. [CrossRef]
16. Boler DE, Uras C, Ince U, Cabioglu N. Factors predicting the nonsentinel lymph node involvement in breast cancer patients with sentinel lymph node metastases. The Breast 2012;21:518-23. [CrossRef]
17. Mustac E, Matusan-Ilijas K, Marijic B, Smokvina M, Jonjic N. Predicting the likelihood of additional nodal metastases in breast carcinoma patients with positive sentinel node biopsy. Int J Surg Pathol 2010;18:36-41. [CrossRef]
18. Fan YG, Tan YY, Wu CT, Treseler P, Lu Y, Chan CW, et al. The effect of sentinel node tumor burden on non-sentinel node status and recurrence rates in breast cancer. Ann Surg Oncol 2005;12:705-11. [CrossRef]
19. Veronesi U, Paganelli G, Viale G, Luini A, Zurrida S, Galimberti V, et al. Sentinel-lymph-node biopsy as a staging procedure in breast cancer:update of a randomised controlled study. Lancet Oncol 2006;7:983-90. [CrossRef]
20. Veronesi U, Paganelli G, Viale G, Luini A, Zurrida S, Galimberti V, et al. A randomized comparison of sentinel-node biopsy with routine axillary dissection in breast cancer. N Engl J Med 2003;349:546-53. [CrossRef]
21. McMasters KM, Tuttle TM, Carlson DJ, Brown CM, Noyes RD, Glaser RL, 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;18:2560-6.
22. Samphao S, Eremin JM, El-Sheemy M, Eremin O. Management of the axilla in women with breast cancer:Current clinical practice and a new selective targeted approach. Ann Surg Oncol 2008;15:1282-96. [CrossRef]
23. Kell MR, Burke JP, Barry M, Morrow M. Outcome of axillary staging in early breast cancer: a meta-analysis. Breast Cancer Res Treat 2010;120:441-7. [CrossRef]
24. Cote RJ, Peterson HF, Chaiwun B, Gelber RD, Goldhirsch A, Castiglione-Gertsch M, et al. Role of immunohistochemical detection of lymph-node metastases in management of breast cancer. International Breast Cancer Study Group. Lancet. 1999;354:896-900. [CrossRef]
25. Giuliano AE, Hunt KK, Ballman KV, Beitsch PD, Whitworth PW, Blumencranz PW, et al. Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis:a randomized clinical trial. JAMA 2011;305(6):569-75. [CrossRef]
26. Schwartz GF. Clinical practice guidelines for the use of axillary sentinel lymph node biopsy in carcinoma of the breast:current update. Breast J 2004;10:85-8. [CrossRef]
27. Straver ME, Meijnen P, van Tienhoven G, van de Velde CJ, Mansel RE, Bogaerts J, et al. Sentinel node identification rate and nodal involvement in the EORTC 10981-22023 AMAROS trial. Ann Surg Oncol 2010;17:1854-61. [CrossRef]
28. Silverstein M, Skinner KA, Lomis TJ. Predicting axillary nodal positivity in 2282 patients with breast carcinoma. World J Surg 2001;25:767-72. [CrossRef]
29. Gajdos C, Tartter PI, Bleiweiss IJ. Lymphatic invasion, tumor size and age are independent predictors of axillary lymph node metastases in women with T1 breast cancers. Ann Surg 1999;230:692-6. [CrossRef]
30. Tjan-Heijnen VC, Pepels MJ, de Boer M, Borm GF, van Dijck JA, van Deurzen CH, et al. Impact of omission of completion axillary lymph node dissection or axillary radiotherapy in breast cancer patients with micrometastases or isolated tumor cells in the sentinel lymph node:results from the MIRROR study. J Clin Oncol 2009;27:18s.
31. Cox C, Vrcel V, Riker A, White L, Allred N, Ramos D, et al. Significance of sentinel lymph node micrometastase on survival for patients with invasive breast cancer. Breast Cancer Res Treat 2005;94(Suppl 1):12-21. van la Parra RF, Ernst MF, Bevilacqua JL, Mol SJ, Van Zee KJ, Broekman JM, et al. Validation of a nomogram to predict the risk of nonsentinel lymph node metastases in breast cancer patients with a positive sentinel node biopsy:validation of the MSKCC breast nomogram. Ann Surg Oncol 2009;16:1128-35. [CrossRef]
32. D’Eredità G, Troilo VL, Giardina C, Napoli A, Rubini G, Fischetti F, et al. Sentinel lymph node micrometastasis and risk of nonsentinel lymph node metastasis:validation of two breast cancer nomograms. Clin Breast Cancer 2010;10:445-51. [CrossRef]
33. Pal A, Provenzano E, Duffy SW, Pinder SE, Purushotham AD. A model for predicting non-sentinel lymph node metastatic disease when the sentinel lymph node is positive. Br J Surg 2008;95:302-9. [CrossRef]
34. Klevesath MB, Pantel K, Agbaje O, Provenzano E, Wishart GC, Gough P, et al. Patterns of metastatic spread in early breast cancer. Breast 2013;22:449-54. [CrossRef]
35. Viale G, Bosari S, Mazzarol G, Galimberti V, Luini A, Veronesi P, et al. Intraoperative examination of axillary sentinel lymph nodes in breast carcinoma patients. Cancer 1999;85:2433-8. [CrossRef]
36. Krishnamurthy S, Meric-Bernstam F, Lucci A, Hwang RF, Kuerer HM, Babiera G, et al. A prospective study comparing touch imprint cytology, frozen section analysis, and rapid cytokeratin immunostain for intraoperative evaluation of axillary sentinel lymph nodes in breast cancer. Cancer 2009;115:1555-62. [CrossRef]
37. Choi YJ, Yun HR, Yoo KE, Kim JH, Nam SJ, Choi YL, et al. Intraoperative examination of sentinel lymph nodes by ultrarapid immunohistochemistry in breast cancer. Jpn J Clin Oncol 2006;36:489-93. [CrossRef]