Azmi Lale, Erhan Aygen, Hatice Nur Lale, Levent Zirek, Merve Zirek, Ali Cihan Yildirir

Factors effecting the development of sentinel lymph node metastasis in clinical early-stage breast cancers (cT1-2N0): Clinical significance of primary tumor – skin distance

Aim: It was aimed to determine the demographic, clinicopathological and radiological predictors that may be effective in the development of sentinel lymph node (SLN) metastasis in patients with clinical early-stage breast cancer (cT1-2N0). Materials and Methods: 178 patients were included in the study. Demographic, clinicopathological and radiological characteristics of the patients were recorded. Among these, there were age, neutrophil / lymphocyte ratio (NLR), HER2, estrogen receptor (ER) and progesterone receptor (PR), proliferation index (Ki- 67), morphological grade, molecular subtype, histopathological subtype, tumor size and localization, multifocality and multicentricity, nipple-areola complex (NAC) infiltration, perineural invasion (PNI), lymphatic invasion (LI), vascular invasion (VI), primary tumor -breast skin distance (DFS). Results: Larger tumor size, HER-2 positivity, grade 3 histopathology, LI, VI, PNI, and closer DFS were found to be significant in univariate regression analyzes. In ROC analysis, the optimum cut-off value for DFS was found to be 13.5mm. In multivariant regression analyzes, HER-2 positivity, LI, PNI and ≤13.5mm DFS were found as independent SLN metastasis predictors. Conclusion: Closer DFS, HER-2 positivity, LI and PNI are very strong predictors in patients with clinical early-stage breast cancer that must be taken into account in the development of SLN metastasis in cT1-2N0 breast cancers. These factors can guide clinicians to take accurate decisions in the treatment process.

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1. Giuliano AE, Ballman KV, McCall L, et al. Effect of Axillary Dissection vs No Axillary Dissection on 10- Year Overall Survival Among Women With Invasive Breast Cancer and Sentinel Node Metastasis: The ACOSOG Z0011 (Alliance) Randomized Clinical Trial. JAMA 2017;318:918-26.
2. Krag DN, Anderson SJ, Julian TB, et al. Sentinellymph-node resection compared with conventional axillary-lymph-node dissection in clinically nodenegative patients with breast cancer: overall survival findings from the NSABP B-32 randomised phase 3 trial. Lancet Oncol 2010;11:927-33.
3. Nguyen TT, Hoskin TL, Habermann EB, et al. Breast Cancer-Related Lymphedema Risk is Related to Multidisciplinary Treatment and Not Surgery Alone: Results from a Large Cohort Study. Ann Surg Oncol 2017;24:2972-80.
4. Zou L, Liu FH, Shen PP, et al. The incidence and risk factors of related lymphedema for breast cancer survivors post-operation: a 2-year follow-up prospective cohort study. Breast Cancer 2018;25:309- 14.
5. Nayyar A, Strassle PD, Shen MR, et al. Survival analysis of early-stage breast cancer patients undergoing axillary lymph node dissection and sentinel lymph node dissection. Am J Surg 2018;216:706-12.
6. Lyman GH, Somerfield MR, Bosserman LD, et al. Sentinel Lymph Node Biopsy for Patients With EarlyStage Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update. J. Clin Oncol 2017;35:561-4.
7. Caywood J, Gray RJ, Hentz J, Pockaj BA. Older age independently predicts a lower risk of sentinel lymph node metastasis in breast cancer. Ann Surg Oncol 2005;12:1061-5.
8. Ding J, Jiang L, Wu W. Predictive Value of Clinicopathological Characteristics for Sentinel Lymph Node Metastasis in Early Breast Cancer. Med Sci Monit 2017;23:4102-8.
9. Fujii T, Yajima R, Tatsuki H, et al. Significance of lymphatic invasion combined with size of primary tumor for predicting sentinel lymph node metastasis in patients with breast cancer. Anticancer Res 2015;35:3581-4.
10. Malter W, Hellmich M, Badian M, et al. Factors Predictive of Sentinel Lymph Node Involvement in Primary Breast Cancer. Anticancer Res 2018;38:3657- 62.
11. Yoo SH, Park IA, Chung YR, et al. A histomorphologic predictive model for axillary lymph node metastasis in preoperative breast cancer core needle biopsy according to intrinsic subtypes. Hum Pathol 2015;46:246-54.
12. Jaime Jans B, Nicolás Escudero M, Dahiana Pulgar B, et al. Clinicopathologic subtypes and compromise of lymph nodes in patients with breast cancer. Ecancermedicalscience 2014;8:448.
13. Reyal F, Rouzier R, Depont-Hazelzet B, et al. The molecular subtype classification is a determinant of sentinel node positivity in early breast carcinoma. PLoS One 2011;6:e20297
14. Mazouni C, Rimareix F, Mathieu MC, et al. Outcome in breast molecular subtypes according to nodal status and surgical procedures. Am J Surg 2013;205:662-7.
15. Houvenaeghel G, Lambaudie E, Classe JM, et al. Lymph node positivity in different early breast carcinoma phenotypes: a predictive model. BMC Cancer 2019;19:45.
16. Torstenson T, Shah-Khan MG, Hoskin TL, et al. Novel factors to improve prediction of nodal positivity in patients with clinical T1/T2 breast cancers. Ann Surg Oncol 2013;20:3286-93.
17. Ansari, B, Morton, MJ, Adamczyk, DL. Distance of breast cancer from the skin and nipple impacts axillary nodal metastases. Ann Surg Oncol 2011;18: 3174-80.
18. Cunningham JE, Jurj AL, Oman L, et al. Is risk of axillary lymph node metastasis associated with proximity of breast cancer to the skin? Breast Cancer Res Treat 2006;100:319-28.
19. Eom YH, Kim EJ, Chae BJ, et al. The distance between breast cancer and the skin is associated with axillary nodal metastasis. J Surg Oncol 2015;111:824-8
20. Amin MB, Greene FL, Edge SB, et al. The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population-based to a more "personalized" approach to cancer staging. CA Cancer J Clin 2017;67:93-9.
21. Coates AS, Winer EP, Goldhirsch A, et al. Tailoring therapies--improving the management of early breast cancer: St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2015. Ann Oncol 2015;26:1533-46.
22. Wolff AC, Hammond ME, Hicks DG, et al. Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. J Clin Oncol 2013;31:3997-4013.
23. Allred DC, Harvey JM, Berardo M, Clark GM. Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Mod Pathol 1998;11:155-68
24. Elston CW, Ellis IO. Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology 1991;19:403-10.
25. Coates AS, Winer EP, Goldhirsch A, et al. Tailoring therapies--improving the management of early breast cancer: St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2015. Ann Oncol 2015;26:1533-46.
26. Anderson WF, Rosenberg PS, Prat A, et al. How many etiological subtypes of breast cancer: two, three, four, or more? J Natl Cancer Inst 2014;106.
27. Denkert C, Budczies J, von Minckwitz G, et al. Strategies for developing Ki67 as a useful biomarker in breast cancer. Breast 2015;24:67-72.
28. Shigematsu H, Nishina M, Yasui D, Hirata T, et al. Minimal prognostic significance of sentinel lymph node metastasis in patients with cT1-2 and cN0 breast cancer. World J Surg Oncol 2019;17:41.
29. Adachi Y, Sawaki M, Hattori M, et al. Comparison of sentinel lymph node biopsy between invasive lobular carcinoma and invasive ductal carcinoma. Breast Cancer 2018;25:560-5.
30. Vandorpe T, Smeets A, Van Calster B, et al. Lobular and non-lobular breast cancers differ regarding axillary lymph node metastasis: a cross-sectional study on 4,292 consecutive patients. Breast Cancer Res Treat 2011;128:429-35.
31. Černá M, Zedníková I, Ňaršanská A, et al. [Avoidance of axillary lymph node dissection in breast cancer patients with metastatic sentinel node - a pilot study]. Rozhl Chir 2015;94:117-25.
32. Harris GC, Denley HE, Pinder SE, et al. Correlation of histologic prognostic factors in core biopsies and therapeutic excisions of invasive breast carcinoma. Am J Surg Pathol 2003;27:11-5.
33. Karak SG, Quatrano N, Buckley J, Ricci A Jr. Prevalence and significance of perineural invasion in invasive breast carcinoma. Conn Med 2010;74:17-21.
34. Duraker N, Caynak ZC, Turkoz K. Perineural invasion has no prognostic value in patients with invasive breast carcinoma. Breast 2006;15:629-34.
35. Colotta F, Allavena P, Sica A, et al. Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability. Carcinogenesis 2009;30:1073-81.
36. Desai AA, Hoskin TL, Day CN, et al. Effect of Primary Breast Tumor Location on Axillary Nodal Positivity. Ann Surg Oncol 2018;25:3011-8.
37. Capdet J, Martel P, Charitansky H, et al. Factors predicting the sentinel node metastases in T1 breast cancer tumor: an analysis of 1416 cases. Eur J Surg Oncol 2009;35:1245-9.
38. D'Alonzo M, Martincich L, Biglia N, et al. Clinical and radiological predictors of nipple-areola complex involvement in breast cancer patients. Eur J Cancer 2012;48:2311-8.
39. Bae MS, Shin SU, Song SE, et al. Association between US features of primary tumor and axillary lymph node metastasis in patients with clinical T1-T2N0 breast cancer. Acta Radiol 2018;59:402-8.
40. Chao C, Edwards MJ, Abell T, et al. Palpable breast carcinomas: a hypothesis for clinically relevant lymphatic drainage in sentinel lymph node biopsy. Breast J 2003;9:26-32.