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Östrojen-Progesteron Reseptörü Pozitif ve Aksiller Lenf Nodu Negatif Meme Kanseri Tanılı Hastalarda Ki-67 Proliferasyon İndeksi

Year 2018, Volume: 10 Issue: 3, 387 - 394, 23.10.2018
https://doi.org/10.18521/ktd.430081

Abstract

Amaç: Ki-67 hücre siklusunda G0 fazı dışında eksprese edilen nükleer bir proteindir. Prolifere olan hücreleri gösteren belirteç olarak kullanılmaktadır. Meme kanseri tanılı hastalarda Ki-67 proliferasyon indeksinin kötü klinik sonuçlarla ilişkili olduğu gösterilmiştir. Bu çalışmada östrojen reseptörü ve progesteron reseptörü pozitif, HER-2 negatif, aksiller lenf nodu tutulumu bulunmayan meme kanseri tanılı hastalarda Ki-67 proliferasyon indeksinin prognostik öneminin değerlendirilmesi amaçlanmıştır.

Gereç ve Yöntem: 2006-2014 yılları arasında tanı konulan ve tıbbi onkoloji kliniğinde izlemi bulunan opere meme kanseri tanılı hastalar çalışmaya dahil edildi. İmmunohistokimyasal olarak nükleer Ki-67 proliferasyon indeksi değerlendirildi. Diğer klinikopatolojik prognostik faktörlerle ilişkisi değerlendirildi.

Bulgular: 162 hasta çalışmaya dahil edildi. Medyan 85 (9-132) aylık izlemde 2 (%1.2) hastada lokal nüks, 7 (%4.3) hastada uzak metastaz saptandı. Sekiz (%4.9) hasta vefat etti. Ki-67 proliferasyon indeksine göre Roc curve analizinde elde edilen %20 değerine göre hastalar iki gruba ayırıldı. Ki-67 proliferasyon indeksi %20’nin altında ve üzerinde olan gruplarda 7 yıllık genel sağkalımlar sırasıyla %97.1 ve %90.9 olarak hesaplandı (p0.042). Ki-67 proliferasyon indeksinin tümör histolojik derecesi, patolojik tümör boyutu ile pozitif korelasyon, hormon reseptörleri ile negatif korelasyon gösterdiği saptandı.

Sonuç: Proliferasyon meme kanserinde prognoz ve tedavi yanıtını predikte etmek için kullanılan önemli bir göstergedir. Ki-67 proliferasyon indeksi için standart eşik değeri bulunmaması, değerlendirme ve skorlama metodolojisinde standart olmamasına rağmen diğer klinikopatolojik prognostik göstergelerle birlikte prognoz belirlenmesinde kullanılmaktadır.

References

  • Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2018. CA Cancer J Clin. 2018; 68(1): 7-30.
  • Sorlie T, Perou C, Tibshirani T, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A. 2001;98(19):10869-74.
  • Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005 May 14-20;365(9472):1687-717.
  • Pertschuk LP, Kim DS, Nayer K, et al. Immunocytochemical estrogen and progestin receptor assays in breast cancer with monoclonal antibodies. Histopathologic, demographic, and biochemical correlations and relationship to endocrine response and survival. Cancer. 1990;66(8):1663-70.
  • Purdie CA, Quinlan P, Jordan LB, et al. Progesterone receptor expression is an independent prognostic variable in early breast cancer: a population-based study. Br J Cancer. 2014;110(3):565-72.
  • Chia S, Norris B, Speers C, et al. Human epidermal growth factor receptor 2 overexpression as a prognostic factor in a large tissue microarray series of node-negative breast cancers. J Clin Oncol. 2008;26(35):5697-704.
  • Carter CL, Allen C, Henson DE .Relation of tumor size, lymph node status, and survival in 24,740 breast cancer cases.Cancer. 1989;63(1):181-7.
  • 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(5):403-10.
  • 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.
  • Gerdes J, Lemke H, Baisch H, et al. Cell cycle analysis of a cell proliferationassociated human nuclear antigen defined by the monoclonal antibody Ki-67. J Immunol 1984;133:1710-15.
  • Lopez F, Belloc F, Lacombe F, et al. Modalities of synthesis of Ki67 antigen during the stimulation of lymphocytes. Cytometry 1991;12:42–9.
  • 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.
  • de Azambuja E, Cardoso F, de Castro G, 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.
  • Criscitiello C, Disalvatore D, De Laurentiis M, et al. High Ki-67 score is indicative of a greater benefit from adjuvant chemotherapy when added to endocrine therapy in luminal B HER2 negative and node-positive breast cancer. Breast 2014;23:69–75.
  • 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.
  • 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 2011. Ann Oncol. 2011;22(8):1736-47.
  • 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 2013. Ann Oncol. 2013;24(9):2206-23.
  • 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(8):1533-46.
  • Dowsett M, Nielsen TO, A'Hern R,et al. Assessment of Ki67 in breast cancer: recommendations from the International Ki67 in Breast Cancer working group. J Natl Cancer Inst. 2011 Nov 16;103(22):1656-64.
  • Liu Y, Yin W, Yan T,et al. The clinical significance of Ki-67 as a marker of prognostic value and chemosensitivity prediction in hormone-receptor-positive breast cancer: a meta-analysis of the published literature. Curr Med Res Opin. 2013;29(11):1453-61.
  • Petrelli2015) Petrelli F, Viale G, Cabiddu M, et al. Prognostic value of different cut-off levels of Ki-67 in breast cancer: a systematic review and meta-analysis of 64,196 patients. Breast Cancer Res Treat. 2015;153(3):477-91.
  • 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(7):e0119565. doi: 10.1371/journal.pone.0119565.
  • Bustreo S, Osella-Abate S, Cassoni P, et al. Optimal Ki67 cut-off for luminal breast cancer prognostic evaluation: a large case series study with a long-term follow-up. Breast Cancer Res Treat. 2016;157(2):363-71.
  • Naito Y, Fujii S, Itoh K, et al. Correlation, comparison, and combined analysis of Ki-67 and histological grade for early luminal breast cancer. American Society of Clinical Oncology Annual Meeting, Chicago, IL, USA, 2012.
  • Sahin AA, Ro J, Ro JY, et al. Ki-67 immunostaining in node-negative stage I/II breast carcinoma. Significant correlation with prognosis. Cancer. 1991;68(3):549-57.
  • 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.
  • 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(2):539-52.
  • Penault-Llorca F, Andre´ F, Sagan C, et al. Ki67 expression and docetaxel efficacy in patients with estrogen receptor-positive breast cancer. J Clin Oncol 2009;27:2809-15.
  • Paik S, Tang G, Shak S, et al. Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer. J Clin Oncol. 2006;24(23):3726-34.
  • Cuzick J, Dowsett M, Pineda S,et al. Prognostic value of a combined estrogen receptor, progesterone receptor, Ki-67, and human epidermal growth factor receptor 2 immunohistochemical score and comparison with the Genomic Health recurrence score in early breast cancer. J Clin Oncol. 2011;29(32):4273-8.
  • Ács B, Kulka J, Kovács KA, et al. Comparison of 5 Ki-67 antibodies regarding reproducibility and capacity to predict prognosis in breast cancer: does the antibody matter? Hum Pathol. 2017;65:31-40.
  • Focke CM, Bürger H, van Diest PJ, et al. Interlaboratory variability of Ki67 staining in breast cancer. Eur J Cancer. 2017;84:219-227.

Ki-67 Labeling Index in Patients with Estrogen-Progesterone Positive and Axillary Lymph Node Negative Breast Cancer

Year 2018, Volume: 10 Issue: 3, 387 - 394, 23.10.2018
https://doi.org/10.18521/ktd.430081

Abstract

Objective: Ki67 is a nuclear protein that is expressed in all phases of the cell cycle except for G0. It is used as a marker to detect the proliferating cells. It has been shown that Ki-67 labeling index is associated with poor clinical outcome in patients with breast cancer. In this study, we aimed to evaluate the prognostic significance of Ki-67 labeling index in patients with estrogen receptor and progesterone receptor positive, HER-2 negative and axillary lymph node negative breast cancer.

Methods: Patients diagnosed with breast cancer during 2006-2014, and who were followed up in the medical oncology clinic were included in the study. Immunohistochemically, nuclear Ki-67 proliferation index was evaluated. The relationship with other clinicopathologic prognostic factors was evaluated.

Results: 162 patients were included in the study. In a median 85 (9-132)-months follow-up, local recurrence was detected in 2(1.2%) patients and distant metastasis was detected in 7(4.3%) patients. Eight (4.9%) patients died. Patients were divided into two groups using 20% cut-off value for Ki-67 labelling index, obtained by Roc curve analysis. The 7-year overall survival was 97.1% in the group with Ki-67 labeling index below 20%, while it was 90.9% in the group above the 20% value (p=0.042). Ki-67 labeling index showed positive correlation with tumor histological grade, and pathologic tumor size, and negative correlation with hormone receptors.

Conclusion: Proliferation is an important indicator for predicting prognosis and treatment response in breast cancer. Ki-67 labeling index is used to determine prognosis along with other clinicopathological prognostic factors, although there is no standard cut-off value and no standard of assessment and no standard in scoring methodology.

References

  • Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2018. CA Cancer J Clin. 2018; 68(1): 7-30.
  • Sorlie T, Perou C, Tibshirani T, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A. 2001;98(19):10869-74.
  • Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005 May 14-20;365(9472):1687-717.
  • Pertschuk LP, Kim DS, Nayer K, et al. Immunocytochemical estrogen and progestin receptor assays in breast cancer with monoclonal antibodies. Histopathologic, demographic, and biochemical correlations and relationship to endocrine response and survival. Cancer. 1990;66(8):1663-70.
  • Purdie CA, Quinlan P, Jordan LB, et al. Progesterone receptor expression is an independent prognostic variable in early breast cancer: a population-based study. Br J Cancer. 2014;110(3):565-72.
  • Chia S, Norris B, Speers C, et al. Human epidermal growth factor receptor 2 overexpression as a prognostic factor in a large tissue microarray series of node-negative breast cancers. J Clin Oncol. 2008;26(35):5697-704.
  • Carter CL, Allen C, Henson DE .Relation of tumor size, lymph node status, and survival in 24,740 breast cancer cases.Cancer. 1989;63(1):181-7.
  • 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(5):403-10.
  • 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.
  • Gerdes J, Lemke H, Baisch H, et al. Cell cycle analysis of a cell proliferationassociated human nuclear antigen defined by the monoclonal antibody Ki-67. J Immunol 1984;133:1710-15.
  • Lopez F, Belloc F, Lacombe F, et al. Modalities of synthesis of Ki67 antigen during the stimulation of lymphocytes. Cytometry 1991;12:42–9.
  • 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.
  • de Azambuja E, Cardoso F, de Castro G, 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.
  • Criscitiello C, Disalvatore D, De Laurentiis M, et al. High Ki-67 score is indicative of a greater benefit from adjuvant chemotherapy when added to endocrine therapy in luminal B HER2 negative and node-positive breast cancer. Breast 2014;23:69–75.
  • 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.
  • 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 2011. Ann Oncol. 2011;22(8):1736-47.
  • 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 2013. Ann Oncol. 2013;24(9):2206-23.
  • 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(8):1533-46.
  • Dowsett M, Nielsen TO, A'Hern R,et al. Assessment of Ki67 in breast cancer: recommendations from the International Ki67 in Breast Cancer working group. J Natl Cancer Inst. 2011 Nov 16;103(22):1656-64.
  • Liu Y, Yin W, Yan T,et al. The clinical significance of Ki-67 as a marker of prognostic value and chemosensitivity prediction in hormone-receptor-positive breast cancer: a meta-analysis of the published literature. Curr Med Res Opin. 2013;29(11):1453-61.
  • Petrelli2015) Petrelli F, Viale G, Cabiddu M, et al. Prognostic value of different cut-off levels of Ki-67 in breast cancer: a systematic review and meta-analysis of 64,196 patients. Breast Cancer Res Treat. 2015;153(3):477-91.
  • 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(7):e0119565. doi: 10.1371/journal.pone.0119565.
  • Bustreo S, Osella-Abate S, Cassoni P, et al. Optimal Ki67 cut-off for luminal breast cancer prognostic evaluation: a large case series study with a long-term follow-up. Breast Cancer Res Treat. 2016;157(2):363-71.
  • Naito Y, Fujii S, Itoh K, et al. Correlation, comparison, and combined analysis of Ki-67 and histological grade for early luminal breast cancer. American Society of Clinical Oncology Annual Meeting, Chicago, IL, USA, 2012.
  • Sahin AA, Ro J, Ro JY, et al. Ki-67 immunostaining in node-negative stage I/II breast carcinoma. Significant correlation with prognosis. Cancer. 1991;68(3):549-57.
  • 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.
  • 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(2):539-52.
  • Penault-Llorca F, Andre´ F, Sagan C, et al. Ki67 expression and docetaxel efficacy in patients with estrogen receptor-positive breast cancer. J Clin Oncol 2009;27:2809-15.
  • Paik S, Tang G, Shak S, et al. Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer. J Clin Oncol. 2006;24(23):3726-34.
  • Cuzick J, Dowsett M, Pineda S,et al. Prognostic value of a combined estrogen receptor, progesterone receptor, Ki-67, and human epidermal growth factor receptor 2 immunohistochemical score and comparison with the Genomic Health recurrence score in early breast cancer. J Clin Oncol. 2011;29(32):4273-8.
  • Ács B, Kulka J, Kovács KA, et al. Comparison of 5 Ki-67 antibodies regarding reproducibility and capacity to predict prognosis in breast cancer: does the antibody matter? Hum Pathol. 2017;65:31-40.
  • Focke CM, Bürger H, van Diest PJ, et al. Interlaboratory variability of Ki67 staining in breast cancer. Eur J Cancer. 2017;84:219-227.
There are 32 citations in total.

Details

Primary Language Turkish
Subjects Health Care Administration
Journal Section Articles
Authors

Betül Bolat Küçükzeybek 0000-0001-6008-5876

Halil Taşkaynatan

Ayşegül Akder Sarı This is me

Seyran Yiğit This is me

Gülden Ballı This is me

Demet Etit This is me

Ayşe Yazıcı This is me

Murat Kemal Atahan

Dilara Özyiğit Büyüktalancı This is me

Ahmet Alacacıoğlu

Yüksel Küçükzeybek

Publication Date October 23, 2018
Acceptance Date September 28, 2018
Published in Issue Year 2018 Volume: 10 Issue: 3

Cite

APA Bolat Küçükzeybek, B., Taşkaynatan, H., Akder Sarı, A., Yiğit, S., et al. (2018). Östrojen-Progesteron Reseptörü Pozitif ve Aksiller Lenf Nodu Negatif Meme Kanseri Tanılı Hastalarda Ki-67 Proliferasyon İndeksi. Konuralp Medical Journal, 10(3), 387-394. https://doi.org/10.18521/ktd.430081
AMA Bolat Küçükzeybek B, Taşkaynatan H, Akder Sarı A, Yiğit S, Ballı G, Etit D, Yazıcı A, Atahan MK, Özyiğit Büyüktalancı D, Alacacıoğlu A, Küçükzeybek Y. Östrojen-Progesteron Reseptörü Pozitif ve Aksiller Lenf Nodu Negatif Meme Kanseri Tanılı Hastalarda Ki-67 Proliferasyon İndeksi. Konuralp Medical Journal. October 2018;10(3):387-394. doi:10.18521/ktd.430081
Chicago Bolat Küçükzeybek, Betül, Halil Taşkaynatan, Ayşegül Akder Sarı, Seyran Yiğit, Gülden Ballı, Demet Etit, Ayşe Yazıcı, Murat Kemal Atahan, Dilara Özyiğit Büyüktalancı, Ahmet Alacacıoğlu, and Yüksel Küçükzeybek. “Östrojen-Progesteron Reseptörü Pozitif Ve Aksiller Lenf Nodu Negatif Meme Kanseri Tanılı Hastalarda Ki-67 Proliferasyon İndeksi”. Konuralp Medical Journal 10, no. 3 (October 2018): 387-94. https://doi.org/10.18521/ktd.430081.
EndNote Bolat Küçükzeybek B, Taşkaynatan H, Akder Sarı A, Yiğit S, Ballı G, Etit D, Yazıcı A, Atahan MK, Özyiğit Büyüktalancı D, Alacacıoğlu A, Küçükzeybek Y (October 1, 2018) Östrojen-Progesteron Reseptörü Pozitif ve Aksiller Lenf Nodu Negatif Meme Kanseri Tanılı Hastalarda Ki-67 Proliferasyon İndeksi. Konuralp Medical Journal 10 3 387–394.
IEEE B. Bolat Küçükzeybek, “Östrojen-Progesteron Reseptörü Pozitif ve Aksiller Lenf Nodu Negatif Meme Kanseri Tanılı Hastalarda Ki-67 Proliferasyon İndeksi”, Konuralp Medical Journal, vol. 10, no. 3, pp. 387–394, 2018, doi: 10.18521/ktd.430081.
ISNAD Bolat Küçükzeybek, Betül et al. “Östrojen-Progesteron Reseptörü Pozitif Ve Aksiller Lenf Nodu Negatif Meme Kanseri Tanılı Hastalarda Ki-67 Proliferasyon İndeksi”. Konuralp Medical Journal 10/3 (October 2018), 387-394. https://doi.org/10.18521/ktd.430081.
JAMA Bolat Küçükzeybek B, Taşkaynatan H, Akder Sarı A, Yiğit S, Ballı G, Etit D, Yazıcı A, Atahan MK, Özyiğit Büyüktalancı D, Alacacıoğlu A, Küçükzeybek Y. Östrojen-Progesteron Reseptörü Pozitif ve Aksiller Lenf Nodu Negatif Meme Kanseri Tanılı Hastalarda Ki-67 Proliferasyon İndeksi. Konuralp Medical Journal. 2018;10:387–394.
MLA Bolat Küçükzeybek, Betül et al. “Östrojen-Progesteron Reseptörü Pozitif Ve Aksiller Lenf Nodu Negatif Meme Kanseri Tanılı Hastalarda Ki-67 Proliferasyon İndeksi”. Konuralp Medical Journal, vol. 10, no. 3, 2018, pp. 387-94, doi:10.18521/ktd.430081.
Vancouver Bolat Küçükzeybek B, Taşkaynatan H, Akder Sarı A, Yiğit S, Ballı G, Etit D, Yazıcı A, Atahan MK, Özyiğit Büyüktalancı D, Alacacıoğlu A, Küçükzeybek Y. Östrojen-Progesteron Reseptörü Pozitif ve Aksiller Lenf Nodu Negatif Meme Kanseri Tanılı Hastalarda Ki-67 Proliferasyon İndeksi. Konuralp Medical Journal. 2018;10(3):387-94.