Prognostic value of the Ki-67 proliferation index in patients with triple negative breast carcinoma. Preliminary report. / Valor pronóstico del índice de proliferación Ki-67 en pacientes con carcinoma de mama triple negativo. Reporte preliminar.

Ángel Fernández, Aldo Reigosa, Felipe Saldivia, Liliana Castillo, Julio Castro

Resumen


Abstract.

The Ki-67 index is a biomarker that indicates the proliferation of cancer cells and is considered an effective prognostic factor for breast cancer. However, a standard cut-off point has not yet been established for the Ki-67 index in triple negative breast carcinomas. Therefore, the objective of this retrospective study was to determine an optimal cut-off point to establish it as a more accurate prognostic factor in the triple negative molecular subtype. The immunohistochemical analysis of the Ki-67 index was performed in 98 patients with breast cancer. The survival study using the Kaplan-Meier method was used to analyze the factors related to overall survival. The cut-off points (20 and 25%) were selected from the univariate analysis because they had the highest Hazard ratio to perform the multivariate analysis. With statistical significance (p<0.001), the analysis revealed that in this series the optimal cut-off point of Ki-67 is 25%, with an independent value regarding the clinicopathological variables considered in the study. These data suggest that the optimal cut-off point at 25% is a more effective prognostic factor for triple negative phenotype breast cancer. Due to the importance of these findings, it is recommended to verify the prognostic value of Ki-67 25% in series with a greater number of patients.

Resumen.

El índice Ki-67 es un biomarcador que indica la proliferación de células cancerosas y se considera un factor pronóstico eficaz para el cáncer de mama. Sin embargo, todavía no se ha establecido un punto de corte estándar para el índice Ki-67 en carcinomas de mama triple negativo. Por lo tanto, el objetivo de este estudio retrospectivo fue determinar un punto de corte óptimo para establecerlo como un factor pronóstico más preciso en el subtipo molecular triple negativo. El análisis inmunohistoquímico del índice Ki-67 se realizó en 98 pacientes con cáncer de mama. Se utilizó el estudio de supervivencia mediante el método de Kaplan-Meier para el análisis de los factores relacionados con la supervivencia global. Los puntos de corte (20 y 25%) fueron seleccionados del análisis univariado por tener el Hazard ratio más alto para realizar el análisis multivariado. Con significancia estadística (p<0,001), el análisis reveló que en esta serie el punto de corte óptimo de Ki-67 es 25%, con valor independiente respecto a las variables clínico-patológicas consideradas en el estudio. Estos datos sugieren que el punto de corte óptimo en 25% es un factor pronóstico más efectivo para el cáncer de mama con fenotipo triple negativo. Por la importancia de estos hallazgos, es recomendable verificar el valor pronóstico de Ki-67 25% en series con un mayor número de pacientes.


Palabras clave


breast carcinoma; proliferation index; Ki-67; carcinoma de mama; índice de proliferación; Ki-67.

Texto completo:

PDF HTML

Referencias


Ács B, Zámbó V, Vízkeleti L, Szász AM, Madaras L, Szentmártoni G, Tőkés T, Molnár BÁ, Molnár IA, Vári-Kakas S, Kulka J, Tőkés AM. Ki-67 as a controver- sial predictive and prognostic marker in breast cancer patients treated with neoad- juvant chemotherapy. Diagn Pathol 2017; 12(1):20-32.

Gui Y, Xu S, Yang X, Gu L, Zhang Z, Luo X, Chen L. A meta-analysis of biomarkers for the prognosis of triple-negative breast cancer patients. Biomark Med 2016; 10(7):771-790.

Tashima R, Nishimura R, Osako T, Nishi- yama Y, Okumura Y, Nakano M, Fujisue M, Toyozumi Y, Arima N. Evaluation of an optimal cut-off point for the Ki-67 index as a prognostic factor in primary breast can- cer: aretrospective study. PLoS One 2015; 10(7):e0119565.

Wu Q, Ma G, Deng Y, Luo W, Zhao Y, Li W, Zhou Q. Prognostic value of Ki-67 in pa- tients with resected triple-negative breast cancer: A Meta-Analysis. Front Oncol 2019; 9:1-9.

Keam B, Im SA, Lee KH, Han SW, Oh DY, Kim JH, Lee SH, Han W, Kim DW, Kim TY, Park IA, Noh DY, Heo DS, Bang YJ. Ki-67 can be used for further classification of tri- ple negative breast cancer into two subty- pes with different response and prognosis. Breast Cancer Res 2011; 13(2):1-7.

Hao S, He ZX, Yu KD, Yang WT, Shao ZM. New insights into the prognostic value of Ki-67 labeling index in patients with triple- negative breast cancer. Oncotarget 2016; 7(17):24824-21831.

Kanyılmaz G, Yavuz BB, Aktan M, Karaağaç M, Uyar M, Fındık S. Prognostic importance of Ki-67 in breast cancer and its relationship with other prognostic factors. Eur J Breast Health 2019; 15(4):256-261.

Coates AS, Winer EP, Goldhirsch A, Ge- lber RD, Gnant M, Piccart-Gebhart M, Thürlimann B, Senn HJ; Panel Members. Tailoring therapies improving the management of early breast cancer: St Gallen Inter- national Expert Consensus on the primary therapy of early breast cancer 2015. Ann Oncol 2015; 26:1533-1546.

Zenzola V, Cabezas-Quintario MA, Arguelles M, Pérez-Fernández E, Izarzugaza Y, Correa A, García-Foncillas J. Prognostic value of Ki-67 according to age in patients with triple-negative breast cancer. Clin Transl Oncol 2018; 20:1448-1454.

Mrklić I, Ćapkun V, Pogorelić Z, Tomić S. Prognostic value of Ki-67 proliferating in- dex in triple negative breast carcinomas. Pathol Res Pract 2013; 209:296-301.

Huang L, Liu Z, Chen S, Liu Y, Shao Z. A prognostic model for triple-negative breast cancer patients based on node sta- tus, cathepsin-D and Ki-67 index. PLoS One 2013; 8(12):e83081.

Fernández Á, Reigosa A, Caleiras E, Sal- divia F, Hardisson D, Sanz F. Cadherins E and P expression in the molecular types of breast cancer. Invest Clin 2015; 56(2):155-168.

Reigosa A, Hardisson D, Sanzi F, Caleiras E, Saldivia F, Fernández A. Subclassifica- tion of the molecular types of breast can- cer based on the expression of immunohis- tochemical markers and evolution. Invest Clin 2016; 57(2):187-216.

Bhargava R, Striebel J, Beriwal S, Flickin- ger JC, Onisko A, Ahrendt G, Dabbs DJ. Prevalence, morphologic features and pro- liferation indices of breast carcinoma mo- lecular classes using immunohistochemical surrogate markers. Int J Clin Exp Pathol 2009; 2:444-455.

Umemura S, Takekoshi S, Susuki Y, Saitoh Y, Tozuda Y, Osamura RY.Estrogen recep- tor-negative and human epidermal growth factor receptor 2-negative breast cancer tissue have the highest Ki-67 labeling index and EGFR expresión: gene amplification does not contribuye to EGFR expresión. Oncol Rep 2005; 14:337-343.

Lee JA, Kim KI, Bae JW, Jung YH, An H, Lee ES, Korean Breast Cancer Society. Tri- plenegative breast cancer in Korea-distinct biology with different impact ofprognostic factors on survival. Breast Cancer Res Treat 2010; 123(1):177-187.

Nishimura R, Osako T, Okumura Y, Ha- yashi M, Toyozumi Y, Arima N. Ki-67 as a prognostic marker according to breast cancer subtype and a predictorof recurren- ce time in primary breast cancer. Exp Ther Med 2010; 1(5):747-754.

Kashiwagi S, Yashiro M, Takashima T, Ao- matsu N, Ikeda K, Ogawa Y, Ishikawa T, Hirakawa K. Advantages of adjuvant che- motherapy for patients with triple-negati- ve breast cancer at Stage II: usefulness of prognostic markers E-cadherin and Ki67. Breast Cancer Res 2011; 13(6):1-12.

Khalifa J, Duprez-Paumier R, Filleron T, Lacroix Triki M, Jouve E, Dalenc F, Mas- sabeau C. Outcome of pN0 triple-negative breast cancer with or without lymph node irradiation: a single institution experience. Breast J 2016; 22(5):510-519.

Liu YX, Wang KR, Xing H, Zhai XJ, Wang LP, Wang W. Attempt towards a novel clas- sification of triple-negative breast cancer using immunohistochemical markers. On- col Lett 2016; 12(2):1240-1256.

Kwon J, Eom KY, Koo TR, Kim BH, Kang E, Kim SW, Park SY, Kim IA. A prognos- tic model for patients with triple-negative breast cancer: importance of the modified nottingham prognostic index and age. J Breast Cancer 2017; 20:65-73.

Najafi S, Mozaffari HR, Sadeghi M. Clini- copathological features of nonmetastatic triple negative breast cancer. Iran J Blood Cancer 2017; 9:18-23.

Jung SY, Han W, Lee JW, Ko E, Kim E, Yu JH, Moon HG, Park IA, Oh DY, Im SA, Kim TY, Hwang KT, Kim SW, Noh DY. Ki-67 ex- pression gives additional prognostic information on St. Gallen 2007 and Adjuvant! Online risk categories in early breast can- cer. Ann Surg Oncol 2009; 16:1112-1121.

Miyashita M, Ishida T, Ishida K, Tamaki K, Amari M, Watanabe M, Ohuchi N, Sa- sano H. Histopathological subclassification of triple negative breast cancer using prog- nostic scoring system: five variables as can- didates. Virchows Arch 2011; 458:65-72.

Aleskandarany MA, Green AR, Benhasou- na AA, Barros FF, Neal K, Reis-Filho JS, Ellis IO, Rakha EA.Prognostic value of pro- liferation assay in the luminal, HER2-po- sitive, and triple-negative biologic classes of breast cancer. Breast Cancer Res 2012; 14(1):1-11.

Zenzola V, Cabezas-Quintario MA, Argue- lles M, Pérez-Fernández E, Izarzugaza Y, Correa A, García-Foncillas J. Prognostic value of Ki-67 according to age in patients with triple-negative breast cancer. Clin Transl Oncol 2018; 20(11):1448-1454.




DOI: http://dx.doi.org/10.22209/IC.v61n2a03

Universidad del Zulia / Venezuela / Investigación Clínica /riclinicas@gmail.com / p-ISSN: 0535-5133 / e-ISSN: 2477-9393

ReviCyHLUZ

Licencia de Creative Commons
Este obra está bajo una licencia de Creative Commons Reconocimiento-NoComercial-CompartirIgual 3.0 Unported.