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Ki 67: a Promising Prognostic Marker in Early Breast Cancer—a Review Article

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Abstract

Ki67 index is considered to be a reliable indicator of the proliferative activity of breast cancer. Additionally, the Ki67 proliferative marker may play a role in assessing response to systemic therapeutic strategies and can act as a prognostic biomarker. But its limited reproducibility which stems from a lack of standardization of procedures, inter-observer variability, and preanalytical and analytical variabilities all have hampered the use of the Ki67 index in clinical practice. Currently, clinical trials have been evaluating Ki67 as a predictive marker for needing adjuvant chemotherapy in luminal early breast cancer patients receiving neoadjuvant endocrine therapy. But the inconsistencies existing in the estimation of the Ki67 index limit the utility of Ki67 in standard clinical practice. The purpose of this review is to evaluate the benefits and drawbacks of utilizing Ki-67 in early-stage breast cancer to prognosticate the disease and predict the risk of recurrence.

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ReferencesQuery

  1. Yersal O, Barutca S (2014) Biological subtypes of breast cancer: prognostic and therapeutic implications. World J Clin Oncol 5:412–424

    Article  PubMed  PubMed Central  Google Scholar 

  2. Dai X, Li T, Bai Z et al (2015) Breast cancer intrinsic subtype classification, clinical use and future trends. Am J Cancer Res 5:2929–2943

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Soliman NA, Yussif SM (2016) Ki-67 as a prognostic marker according to breast cancer molecular subtype. Cancer Biol Med 13:496–504

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Onitilo AA, Engel JM, Greenlee RT et al (2009) Breast cancer subtypes based on ER/PR and Her2 expression: comparison of clinicopathologic features and survival. Clin Med Res 7:4–13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Liang Q, Ma D, Gao RF et al (2020) Effect of Ki-67 expression levels and histological grade on breast cancer early relapse in patients with different immunohistochemical-based subtypes. Sci Rep 10:7648

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Kunheri B, Raj RV, Vijaykumar DK et al (2020) Impact of St. Gallen surrogate classification for intrinsic breast cancer sub-types on disease features, recurrence, and survival in south Indian patients. Indian J Cancer 57:49–54

    Article  PubMed  Google Scholar 

  7. Vijaykumar DK, Arun S et al (2019) Breast cancer care in south India: is practice concordant with national guidelines? J Glob Oncol 5:1–7

    CAS  PubMed  Google Scholar 

  8. Li LT, Jiang G, Chen Q, Zheng JN (2014) Ki67 is a promising molecular target in the diagnosis of cancer (review). Mol Med Rep 11:1566–1572

    Article  PubMed  Google Scholar 

  9. Dowsett M, Nielsen TO, A’Hern R et al (2011) Assessment of Ki67 in breast cancer: recommendations from the International Ki67 in Breast Cancer working group. J Natl Cancer Inst 103:1656–1664

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Sun X, Kaufman PD (2018) Ki-67: more than a proliferation marker. Chromosoma 127:175–186

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Zhu X, Chen L, Huang B et al (2020) The prognostic and predictive potential of Ki-67 in triple-negative breast cancer. Sci Rep 10:225

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Fragomeni SM, Sciallis A, Jeruss JS (2018) Molecular subtypes and local-regional control of breast cancer. Surg Oncol Clin N Am 27:95–120

    Article  PubMed  PubMed Central  Google Scholar 

  13. Korde LA, Somerfield MR, Carey LA et al (2021) Neoadjuvant chemotherapy, endocrine therapy, and targeted therapy for breast cancer: ASCO guideline. J Clin Oncol 39:1485–1505

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Smith I, Robertson J, Kilburn L et al (2020) Long-term outcome and prognostic value of Ki67 after perioperative endocrine therapy in postmenopausal women with hormone-sensitive early breast cancer (POETIC): an open-label, multicentre, parallel-group, randomized, phase 3 trial. Lancet Oncol 21:1443–1454

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Nielsen TO, Leung SCY, Rimm DL et al (2021) Assessment of Ki67 in breast cancer: updated recommendations from the International Ki67 in Breast Cancer Working Group. J Nat Cancer Inst 113:808–819

    Article  PubMed  Google Scholar 

  16. Arthur LM, Turnbull AK, Khan LR et al (2017) Pre-operative endocrine therapy. Curr Breast Cancer Rep 9:202–209

    Article  PubMed  PubMed Central  Google Scholar 

  17. Ellis MJ, Suman VJ, Hoog J et al (2017) Ki67 proliferation index as a tool for chemotherapy decisions during and after neoadjuvant aromatase inhibitor treatment of breast cancer: results from the American College of Surgeons Oncology Group Z1031 Trial (Alliance). J Clin Oncol 35:1061–1069

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Suman VJ, Ellis MJ, Ma CX (2015) The ALTERNATE trial: assessing a biomarker driven strategy for the treatment of post-menopausal women with ER+/Her2- invasive breast cancer. Chin Clin Oncol 4:34

    PubMed  PubMed Central  Google Scholar 

  19. Dowsett M, Smith IE, Ebbs SR et al (2005) 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. Clinical Cancer Research : An Official Journal of the American Association for Cancer Research 11:951s–8s

  20. Vaz-Luis I, O’Neill A, Sepucha K et al (2017) Survival benefit needed to undergo chemotherapy: patient and physician preferences. Cancer 123:2821–2828

    Article  CAS  PubMed  Google Scholar 

  21. Walsh EM, Smith KL, Stearns V (2020) Management of hormone receptor-positive, HER2-negative early breast cancer. Semin Oncol 47:187–200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Choudhari AS, Mandave PC, Deshpande M et al (2020) Phytochemicals in cancer treatment: from preclinical studies to clinical practice. Front Pharmacol 10:1614

    Article  PubMed  PubMed Central  Google Scholar 

  23. Guerrero-Zotano AL, Arteaga CL (2017) Neoadjuvant trials in ER+ breast cancer: a tool for acceleration of drug development and discovery. Cancer Discov 7:561–574

    Article  PubMed  PubMed Central  Google Scholar 

  24. Al-Mahmood S, Sapiezynski J, Garbuzenko OB et al (2018) Metastatic and triple-negative breast cancer: challenges and treatment options. Drug Deliv Transl Res 8:1483–1507

    Article  PubMed  PubMed Central  Google Scholar 

  25. Viral P, Keechilat P, Beena K et al (2021) Ten-year survival outcome of breast cancer patients in India. J Carcinog 20:1

    Article  PubMed  PubMed Central  Google Scholar 

  26. Buus R, Sestak I, Kronenwett R et al (2021) Molecular drivers of oncotype DX, prosigna, EndoPredict, and the breast cancer index: A TransATAC study. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology 39:126–135

    Article  CAS  PubMed  Google Scholar 

  27. Chalkidou A, Landau DB, Odell EW et al (2012) Correlation between Ki-67 immunohistochemistry and 18F-fluorothymidine uptake in patients with cancer: a systematic review and meta-analysis. Eur J Cancer 48:3499–3513

    Article  CAS  PubMed  Google Scholar 

  28. Davey MG, Hynes SO, Kerin MJ et al (2021) Ki-67 as a prognostic biomarker in invasive breast cancer. Cancers 13:4455

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Rui G, Li M, Xiomei B et al (2021) Scoring method for immunohistochemical staining on Ki67. Appl Immunohistochem Mol Morphol 29:e20–e28

    Google Scholar 

  30. Khoury T (2018) Delay to formalin fixation (cold ischemia time) effect on breast cancer molecules. Am J Clin Pathol 149:275–292

    Article  CAS  PubMed  Google Scholar 

  31. Polley MY, Leung SC, McShane LM et al (2013) International Ki67 in Breast Cancer Working Group of the Breast International Group and North American Breast Cancer Group (2013). An international Ki67 reproducibility study. J Natl Cancer Inst 105:1897–1906

    Article  PubMed  PubMed Central  Google Scholar 

  32. Ki67 IHC mib-1-pharmdx (dakoomnis)- P210026. https://www.fda.gov/medical-devices/recently-approved-devices/ki-67-ihc-mib-1-pharmdx-dako-omnis-p210026. Accessed 23 Mar 2022

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Author notes

  1. Lakshmi Malavika Nair, Archana George Vallonthaiel, and M. P. Narmadha contributed equally as joint second authors.

Authors and Affiliations

  1. Department of Pharmacy Practice, Amrita School of Pharmacy, Amrita Institute of Medical Science and Research Centre, AIMS-Ponekkara, Amrita Vishwa Vidyapeetham, Kochi, Kerala, 682041, India

    Dhanya Mary Louis & M. P. Narmadha

  2. Breast Diseases Division, Amrita School of Medicine, Amrita Institute of Medical Science and Research Centre, AIMS-Ponekkara, Amrita Vishwa Vidyapeetham, Kochi, Kerala, 682041, India

    Lakshmi Malavika Nair & D. K. Vijaykumar

  3. Department of Pathology, Amrita School of Medicine, Amrita Institute of Medical Science and Research Centre, AIMS-Ponekkara, Amrita Vishwa Vidyapeetham, Kochi, Kerala, 682041, India

    Archana George Vallonthaiel

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  1. Dhanya Mary Louis
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  2. Lakshmi Malavika Nair
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Correspondence to D. K. Vijaykumar.

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Louis, D.M., Nair, L.M., Vallonthaiel, A.G. et al. Ki 67: a Promising Prognostic Marker in Early Breast Cancer—a Review Article. Indian J Surg Oncol 14, 122–127 (2023). https://doi.org/10.1007/s13193-022-01631-6

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  • DOI: https://doi.org/10.1007/s13193-022-01631-6

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