Meriç Emre BOSTANCI, Kürşat KARADAYI, Murat Can MOLLAOĞLU

The relationship between Ki-67 index and axillary lymph node metastasis in breast carcinoma

Aim: Breast cancer is the most common type of cancer in women. The presence and number of metastatic lymph nodes in the axillaare the most signifiant prognostic factors in breast cancer. In addition, tumor size, lymphovascular invasion, perineural invasion,histopathological type and grade of the tumor are among the best-known prognostic factors. Ki-67 is expressed in G1, S, G2 andM phases of the cell cycle but not in the G0 phase, which allows it to be used as a marker for proliferating cells. The purpose ofthis study is to determine the relationship between Ki-67 Index and classical prognostic factors in breast cancer patients and toinvestigate its effect on axillary lymph node metastasis.Material and Methods: 46 patients, who were diagnosed as breast carcinoma in Sivas Cumhuriyet University Medical Faculty SurgicalOncology Department and who underwent a modifid radical mastectomy and axillary lymph node dissection between 2017 and2019 were included in this study. Histological tumor type, stage, status of axillary lymph nodes and Ki-67 Index were evaluatedretrospectively from the pathology reports of the patients. The patients were grouped under three categories according to Ki-67Index.Results: Regarding the grouping of the patients according to Ki-67 Index, the ones below 15% formed the fist group, between 15-29% the second group, and above 30% the third group. The distribution of the patients according to negativity-positivity of axillarylymph node metastasis in the groups was as fallow: First group, 7 (41.2%) negative - 10 (58.8%) positive; Second group 4 (33.3%)negative - 8 (66.7%) positive; Third Group 3 (17.6%) negative - 14 (82.4%) positive. Of the 46 patients included in the study, 14 (30.4%)were negative for axillary lymph node metastasis and 32 (69.9%) were positive. In our study, the relationship between the increaseof Ki-67 Index and axillary lymph node positivity was found to be statistically signifiant.Conclusion: In this study, we investigated the relationship between Ki-67 Index and classical prognostic markers, especially lymphnode metastasis. Proliferation is an important indicator used to predict prognosis and treatment response in breast cancer. In ourstudy, Ki-67 Index, one of the cell proliferation markers, was found to be positively correlated with axillary lymph node metastasisand other prognostic factors. Therefore, Ki-67 Index was shown to be a signifiant prognostic indicator in breast cancer.

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1. Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin 2011;61:69-90.
2. Siegel RL, Miller KD, Jemal A. Cancer statistics. CA Cancer J Clin 2015;65:5-29.
3. Parkin DM, Bray F, Ferlay J, et al. Estimating the world cancer burden: Globocan 2000. Int J Cancer 2001;15:153-6.
4. Wooster R, Weber BL. Breast and ovarian cancer. N Engl J Med. 2003;348:2339-47.
5. Cianfrocca M, Goldstein LJ. Prognostic and predictive factors in early-stage breast cancer. The Oncologist 2004;9:606-16.
6. Dees EC, Lawrence N, Souba WW, et al. Does Information From Axillary Dissection Change Treatment In Clinically Node-Negative Patients With Breast Cancer. Ann Surg 1999;226:279-87.
7. Anderson BO, Austin-Seymour M.M, Gralow JR, et al. A Multidisciplinary Approach to Locoregional Management of the Axilla for Primary Operable Breast Cancer. Cancer Control 1997;4:491-9.
8. Barth RJ, Danforth DN, Venzon DJ, et al. Level of Axillary Involvement by Lymph Node Metastases From Breast Cancer is not An Independent Predictor of Survival. Arch Surg 1999;126:574-77.
9. Gerdes J, Schwab U, Lemke H, et al. Production of a Mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation. Int J Cancer 1983;31:13-20.
10. Gerdes J, Lemke H, Baisch H, et al. Cell cycle analysis of a cell proliferationassociated human nuclear antigen defied by the monoclonal antibody Ki-67. J Immunol 1984;133:1710-5.
11. Trihia H, Murray S, Price K, et al. Ki-67 expression in breast carcinoma: its association with grading system, clinical parameters, and other prognostic factors-a surrogate marker? Cancer 2003;97:1321-31.
12. de Azambuja E, Cardoso F, de Castro G Jr, et al. Ki- 67 as prognostic marker in early breast cancer: a meta-analysis of published studies involving 12,155 patients. Br J Cancer 2007;96:1504-13.
13. Criscitiello C, Disalvatore D, De Laurentiis M, et al. High Ki-67 score is indicative of a greater benefi from adjuvant chemotherapy when added to endocrine therapy in luminal B HER2 negative and node-positive breast cancer. Breast 2014;23:69-75.
14. Denkert C, Loibl S, Müller BM, et al. Ki67 levels as predictive and prognostic parameters in pretherapeutic breast cancer core biopsies: a translational investigation in the neoadjuvant GeparTrio trial. Ann Oncol 2013;24:2786-93.
15. Goldhirsch A, Wood WC, Coates AS, et al. Strategies for subtypes--dealing with the diversity of breast cancer: highlights of the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer. Ann Oncol 2011;22:1736-47.
16. Goldhirsch A, Winer EP, Coates AS, et al. Personalizing the treatment of women with early breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer. Ann Oncol 2013;24:2206-23.
17. Urru SAM, Gallus S, Bosetti C et al. Clinical and pathological factors influencing survival in a large cohort of triple-negative breast cancer patients. BMC Cancer 2018;18:56.
18. Luo A, Wu F, Han R et al. Clinicopathological features and prognostic evaluation of bone metas-tasis in triple-negative breast cancer. J Cancer Res Ther 2017; 13:778-84.
19. Peiris H, Mudduwa L, Thalagala N, Jayatialake K. The value of Nottingham grade in breast cancer re-visited in the Sri Lankan setting. Malays J Pathol 2017;39: 141-8.
20. Freitas RJ, Nunes RD, Martins E, et al. Prog-nostic factors and overall survival of breast cancer in the city of Goiania, Brazil: a population-based study. Rev Col Bras Cir. 2017;44:435-43.
21. Kondov B, Isijanovska R, Milenkovikj Z et al. Impact of size of the tumour, persistence of estro-gen receptors, progesterone receptors, HER2Neu receptors and Ki67 values on positivity of axillary lymph nodes in patients with early breast cancer with clinically negative axillary examination. Open Access Maced J Med Sci 2017;5:825-30.
22. Tashima R, Nishimura R, Osako T, et al. Evaluation of an Optimal Cut-Off Point for the Ki-67 Index as a Prognostic Factor in Primary Breast Cancer: A Retrospective Study. PLoS One 2015;10:0119565.
23. Trihia H, Murray S, Price K, et al. International Breast Cancer Study Group. Ki-67 expression in breast carcinoma: its association with grading systems, clinical parameters, and other prognostic factors-a surrogate marker? Cancer 2003;97:1321-31.
24. Li CI, Anderson BO, Daling JR, Moe RE. Trends in incidence rates of invasive lobular and ductal breast carcinoma. Jama. 2003;289:1421-4.
25. Viale G, Regan MM, Mastropasqua MG, et al. Predictive value of tumor Ki-67 expression in two randomized trials of adjuvant chemoendocrine therapy for node-negative breast cancer. J Natl Cancer Inst 2008;100:207-12.
26. Inwald EC, Klinkhammer-Schalke M, Hofstädter F,et al. Ki-67 is a prognostic parameter in breast cancer patients: results of a large population-based cohort of a cancer registry. Breast Cancer Res Treat 2013;139:539-52.
27. Lee AK, Loda M, Mackarem G, et al. Lymph node negative invasive breast carcinoma 1 centimeter or less in size (T1a,bN0M0): clinicopathologic features and outcome. Cancer 1997;79:761-71.
28. Rosen PP, Groshen S, Kinne D, et al. Factors influencing prognosis in node-negative breast carcinoma: analysis of 767 T1N0M0/T2N0M0 patients with longterm follow-up. J Clin Oncol 1993;11:2090-100.
29. Sahin AA, Ro J, Ro JY, et al. Ki-67 immunostaining in node-negative stage I/II breast carcinoma. Signifiant correlation with prognosis. Cancer 1991;68:549-57.