Ki-67: role in diagnosis, prognosis and follow-up after treatment of breast cancers

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Published Jan 18, 2016
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Vol. 93 No. 12 (2015): Issue Dec 2015

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Houda El Benna
Aref Zribi
Soumaya Laabidi
Abderrazek Haddaoui
Mouna Mlika
Hela Skhiri
Mahdi Afrit
Khaled Rahal
Hammouda Boussen

Abstract

SUMMARY
Aim : To evaluate the literature data about diagnostic value, prognosis value and interest in follow-up of Ki-67 antibody after treatment for breast cancer.
Methods: We performed a literature search in pubmed using the keywords : Ki-67, anti-Ki-67, breast cancer, prognosis, proliferation, chemotherapy, hormone therapy.
Results: Ki-67 is routinely used as a static marker of proliferative activity and in follow-up-monitoring before and after treatment by chemotherapy and more recently hormonotherapy. Ki-67 was also used at a cut-off of 14% to differentiate between luminal A and B breast cancers. A high Ki-67 expression is probably related to a poorer prognosis but also a better response to neoadjuvant chemo and/or targeted therapy. More recently, genomic analysis is more reliable to classify the molecular breast cancer subtypes avoiding the possible cases of discordant Ki-67 rate. Ki-67 is also interesting in predicting histological response to neoadjuvant chemo and hormone therapy.
Conclusion: Ki-67 evaluated by immunohistochemistry is important in routine in countries without bimolecular plateforms despite technical insufficiencies. When available, genomic grading is better to classify molecular subtypes and determine breast cancer prognosis in adjuvant and neoadjuvant setting.

Keywords:

Ki67 antibody, breast cancer, prognosis, proliferation, chemotherapy, hormone therapy, targeted therapy.

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References

  1. World Health organization. International agency for research on Cancer. WORLD CANCER REPORT 2012. Globocan.
  2. Maalej M, Hentati D, Messai T et al. Breast cancer in Tunisia in 2004: a comparative clinical and epidemiological study. Bull Cancer 2008; 95:5-9.
  3. Ben Abdallah M, Zehani S, Maalej M et al. Cancer du sein en Tunisie: caractéristiques épidémiologiques et tendance évolutive de l'incidence. Tunis Med 2009;87:417-425.
  4. Gerdes J, Li L, Schlueter C et al. Immunobiochemical and molecular biologic characterization of the cell proliferation-associated nuclear antigen that is defined by monoclonal antibody Ki-67. Am J Pathol 1991; 138:867-873.
  5. Bridger JM, Kill IR, Lichter Pand et al. Association of pKi-67 with satellite DNA of the human genome in early G1 cells. Chromosome Res 1998; 6:13-24.
  6. MacCallum DE, Hall PA. The biochemical characterization of the DNA binding activity of Ki 67. J Pathol. 2000; 191:286-98.
  7. Ekholm M, Beglerbegovic S, Grabau D et al. Immunohistochemical assessment of Ki67 with antibodies SP6 and MIB1 in primary breast cancer: a comparison of prognostic value and reproducibility. Histopathology 2014; 65:252-60.
  8. Tsuda H, Akiyama F, Kurosumi M et al. Evaluation of the interobserver agreement in the number of mitotic figures of breast carcinoma as simulation of quality monitoring in the Japan National Surgical Adjuvant Study of Breast Cancer protocol. Jpn J Cancer Res 2000; 91:451-457.
  9. F. Penault-Llorca, André F, Sagan C et al. Ki67 expression and docetaxel efficacy in patients with estrogen receptor-positive breast cancer. J Clin Oncol 2009; 10:2809-15.
  10. Ying M, He Y, Qi M et al. Value of pre-treatment biomarkers in prediction of response to neoadjuvant endocrine therapy for hormone receptorpositive postmenopausal breast cancer. Chin J Cancer Res. 2013; 25:397-404.
  11. Dowsett M, Smith IE, Ebbs SR et al. Short-term changes in Ki-67 during neoadjuvant treatment of primary breast cancer with anastrozole or tamoxifen alone or combined correlate with recurrence-free survival. Clin Cancer Res 2005; 11:951-8.
  12. Yamamoto S, Chishima T, Mastubara Y et al. Variability in measuring the ki-67 labeling index in patients with breast cancer. Clin Breast Cancer 2015; 15:35-39.
  13. 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: 1504-1513.
  14. Stuart-Harris R, Caldas C, Pinder SE et al. Proliferation markers and survival in early breast cancer: a systematic review and meta-analysis of 85 studies in 32,825 patients. Breast 2008; 17: 323-334.
  15. Keshgegian AA, Cnaan A. Proliferation markers in breast carcinoma. Mitotic figure count, S-phase fraction, proliferating cellnuclear antigen, Ki- 67 and MIB-1. Am J Clin Pathol 1995; 104:42-9.
  16. Li FY, Wu SG, Zhou J et al. Prognostic value of Ki-67 in breast cancer patients with positive axillary lymph nodes: A retrospective cohort study. PLoS One 2014; 9(2).
  17. Li H, Han X, Liu Yand al. Ki67 as a predictor of poor prognosis in patients with triple- negative breast cancer. Oncol Lett 2015; 9:149-152.
  18. Kilickap S, Kaya Y, Yucel B et al. Higher Ki67 expression is associates with unfavorable prognostic factors and shorter survival in breast cancer. Asian Pac J Cancer Prev 2014; 15:1381-5.
  19. Cheang MC, Chia SK, Voduc D et al. Ki67 index, HER2 status and prognosis of patients with luminal B breast cancer. J Natl Cancer Inst 2009; 101:736-50.
  20. Vachon CM, Schaid DJ, Ingle JN et al. Apolygenic risk score for breast cancer in women receiving tamoxifen or raloxifene on NSABP P-1 and P- 2. Breast Cancer Res Treat 2015;149:517-23.
  21. Goldhirsch A, Winer EP, Coates AS, Gelber RD, Piccart-Gebhart ,Thürlimann B, Senn HJ; Panel members. 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; 24:2206-23.
  22. Goldhirsch A, Wood WC, Coates AS, Gelber RD, Thürlimann B, Senn HJ; Panel members. 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; 22:1736-47.
  23. Peter A Fasching, Katharina Heusinger, Lothar Haeberle et al. Ki67, chemotherapy response, and prognosis in breast cancer patients receiving neoadjuvant treatment. BMC Cancer 2011; 11:486.
  24. Guarneri V, Piacentini F, Ficarra G et al. A prognostic model based on nodal status and Ki-67 predicts the risk of recurrence and death in breast cancer patients with residual disease after preoperative chemotherapy. Ann Oncol 2009; 20:1193-8.
  25. Kim MK, Han W, Moon HG et al. Nomogram for Predicting Breast Conservation after Neoadjuvant Chemotherapy. Cancer Res Treat 2014; 46:374-382.
  26. Horimoto Y, Arakawa A, Tanabe M et al. Ki67 expression and the effect of neo- adjuvant chemotherapy on luminal HER2-negative breast cancer. BMC Cancer 2014; 14:550.
  27. Petit T, Wilt M, Velten M and al. Comparative value of tumour grade, hormonal receptors,Ki-67, HER-2 and topoisomerase II alpha status as predictive markers in breast cancer patients treated with neoadjuvant anthracycline-based chemotherapy. Eur J Cancer 2004; 40:205-11.
  28. Faneyte IF, Schrama JG, Peterse JL, Remijnse PL, Rodenhuis S, van de Vijver MJ. Breast cancer response to neoadjuvant chemotherapy: predictive markers and relation with outcome. Br J Cancer 2003; 88:406- 12.
  29. Sueta A, Yamamoto Y, Hayashi M et al. Clinical significance of pretherapeutic Ki67 as a predictive parameter for response to neoadjuvant chemotherapy in breast cancer: is it equally useful across tumor subtypes? Surgery 2014; 155:927-35.
  30. 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.
  31. Smith IE, Dowsett M, Ebbs SR et al. IMPACT Trialists Group. Neoadjuvant treatment of postmenopausal breast cancer with anastrozole, tamoxifen, or both in combination: the Immediate Preoperative Anastrozole, Tamoxifen, or Combined with Tamoxifen (IMPACT) multicenter double-blind randomized trial. J Clin Oncol 2005;1;23:5108-16.
  32. Cuzick J, Sestak I, Baum M et al. ATAC/LATTE investigators. Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 10-year analysis of the ATAC trial. Lancet Oncol 2010;11:1135-41.
  33. Palmieri C, Cleator S, Kilburn LS et al. NEOCENT: a randomised feasibility and translational study comparing neoadjuvant endocrine therapy with chemotherapy in ER-rich postmenopausal primary breast cancer. Breast Cancer Res Treat 2014; 148:581-90.
  34. Jalava P, Kuopio T, Juntti-Patinen L, Kotkansalo T, Kronqvist P, Collan Y. Ki 67 immunohistochemistry: a valuable marker in prognostication but with a risk of misclassification: proliferation subgroups formed based on Ki67 immunoreactivity and standardized mitotic index. Histopathology 2006; 48:674-82.
  35. Bertucci F, Finetti P, Roche H et al. Comparison of the prognostic value of genomic grade index, Ki 67 expression and mitotic activity index in early node-positive breast cancer patients. Ann Oncol 2013;24:625-32.
  36. Yerushalmi R, Woods R, Ravdin PM, Hayes MM, Gelmon KA. Ki67 in breast cancer: prognostic and predictive potential. Lancet Oncol 2010; 11:174-83.