Iranian Journal of Pathology

Prognostic Significance of Reduction in Ki67 Index After Neoadjuvant Chemotherapy in Patients With Breast Cancer in Kerman Between 2009 And 2014

Document Type : Original Research

Authors

Vahid Moazed 1
Elham Jafari 2
Behjat Kalantari khandani 1
Ali Nemati 1
seyedamir benrazavi 3

1 Hematology and Oncology Division, Dept of Internal medicine, Afzalipour Kerman Medical Science University, Kerman, Iran

2 Pathology and Stem Cells Research Center, Dept of Pathology, Afzalipour Kerman Medical Science University, Kerman, Iran

3 Dept. of Internal Medicine, Afzalipour Kerman Medical Science University, Kerman, Iran

https://doi.org/10.30699/ijp.13.1.71
Abstract
Background and objective:Breast cancer is the most common malignancy among women. The Neoadjuvant chemotherapy is the treatment of choice for non-operable tumors. The Ki67 is a proliferation marker that can be used to predict the therapeutic response to chemotherapy and the patients' prognosis.
Methods: This retrospective study was carried out on 55 consecutive patients with breast cancer referred to a Training Tertiary Healthcare Center in Kerman, Iran since 2009 to 2014. After diagnostic approval, the tissue samples of patients were examined for estrogen and progesterone receptors, ki67 and HER2-neu markers by using immunohistochemical staining. Then the patients were treated with 6 cycles of Neoadjuvant chemotherapy regimens by Doxorubicin and Taxans or 4 chemotherapy cycles, containing Anthracycline and Cyclophosphamide and 4 cycles of Paclitaxel. After mastectomy, their samples were reexamined for ki67 again and classified into three groups (low: ki67<15%), medium (Ki67 = 16-30%) and high (Ki67> 30%).
Results: Before chemotherapy, 54.5% of the patients had high expression of Ki67. But after chemotherapy, 52.7 of the patients had complete therapeutic response showing that the Ki67 level was reduced significantly (P=0.003).
Conclusion: Before and after Neoadjuvant chemotherapy, Ki67 measurements may be used as a predictive marker of therapeutic response.

Keywords

Neoadjuvant Therapy
Ki 67
Breast cancer
Prognosis

Subjects

  1. Amani D, Hassan ZM, Ravangard F, Frazmand S, Karim-Zadeh M. Flowcytometric Analysis of Tumor Associated Macrophages in Invasive Ductal Carcinoma of Breast. Iranian J Immunol. 2005; 2:117-22.
  2. Cooksley S, Hipkiss JB, Tickle SP, Holmes-Ievers E, Docherty AJ, Murphy G, et al. Immunoassays for the Detection of Human Collagenase, Stromelysin, Tissue Inhibitor of Metallo-proteinases (TIMP) and Enzyme-Inhibitor Complexes. Matrix. 1990;10(5):285-91.
  3. Newman PJ. The Role of PECAM-1 in Vascular Cell Biologya. Annals of the New York Academy of Sciences. 1994; 714(1):165-74.
  4. Luukkaa M, Vihinen P, Kronqvist P, Vahlberg T, Pyrhönen S, Kähäri VM, et al. Association between high collagenase-3 expression levels and poor prognosis in patients with head and neck cancer. Head & neck. 2006 Mar 1;28(3):225-34.
  5. Jones RL, Smith IE. Neoadjuvant treatment for early-stage breast cancer: opportunities to assess tumour response. The lancet oncology. 2006 Oct 31;7(10):869-74
  6. Kim KI, Lee KH, Kim TR, Chun YS, Lee TH, Park HK. Ki-67 as a predictor of response to neoadjuvant chemotherapy in breast cancer patients. Journal of breast cancer. 2014 Mar 1;17 (1):40-6.
  7. Juhasz-Böss I, Mavrova R, Moga S, Radosa J, Schmidt G, Bohle RM, et al. Solomayer E, Herr D. Can Ki-67 Play a Role in Prediction of Breast Cancer Patients' Response to Neoadjuvant Chemotherapy. BioMed Research International. 2014; 2014.
  8. Urruticoechea A, Smith IE, Dowsett M. Proliferation marker Ki-67 in early breast cancer. Journal of clinical oncology. 2005; 23(28):7212-20.
  9. Archer CD, Parton M, Smith IE, Ellis PA, Salter J, Ashley S,et.al. Early changes in apoptosis and proliferation following primary chemotherapy for breast cancer. British journal of cancer. 2003; 89(6):1035-41.
  10. Ellis PA, Smith IE, Detre S, Burton SA, Salter J, A'hern R, et al. Reduced apoptosis and proliferation and increased Bcl-2 in residual breast cancer following preoperative chemotherapy. Breast cancer research and treatment. 1998; 48(2):107-16.
  11. Avci N, Deligonul A, Tolunay S, Cubukcu E, Olmez OF, Ulas A, et al. Neoadjuvant chemotherapy-induced changes in immunohistochemical expression of estrogen receptor, progesterone receptor, HER2, and Ki-67 in patients with breast cancer. J. BUON. 2015; 20:45-9.
  12. Tanei T, Shimomura A, Shimazu K, Nakayama T, Kim SJ, Iwamoto T, et al. Prognostic significance of Ki67 index after neoadjuvant chemotherapy in breast cancer. European Journal of Surgical Oncology (EJSO). 2011; 37(2):155-61.
  13. Jones RL, Salter J, A’Hern R, Nerurkar A, Parton M, Reis-Filho et al. The prognostic significance of Ki67 before and after neoadjuvant chemotherapy in breast cancer. Breast cancer research and treatment. 2009; 116(1):53-68.
  14. von Minckwitz G, Schmitt WD, Loibl S, Müller BM, Blohmer JU, Sinn BV, et al. Ki67 measured after neoadjuvant chemotherapy for primary breast cancer. Clinical Cancer Research. 2013; 19(16):4521-31.
  15. Dowsett M, Smith IE, Ebbs SR, Dixon JM, Skene A, A'Hern R, et al. Prognostic value of Ki67 expression after short-term presurgical endocrine therapy for primary breast cancer. Journal of the National Cancer Institute. 2007; 99(2):167-70.
  16. Sun J, Chen C, Wei W, Zheng H, Yuan J, Tu Y, et al. Associations and indications of Ki67 expression with clinicopathological parameters and molecular subtypes in invasive breast cancer: A population-based study. Oncology letters. 2015; 10(3):1741-8.
  17. Haroon S, Hashmi AA, Khurshid A, Kanpurwala MA, Mujuba S, Malik B. Ki67 index in breast cancer: correlation with other prognostic markers and potential in pakistani patients. Asian Pac J Cancer Prev. 2013; 14(7):4353-8.
  18. Sharifi SN, Sadeghian F, Homaei SF, Haghighi F. Immunohistochemical study of cell proliferation marker (ki-67), estrogen, and progesterone receptors expression in breast carcinoma.Birjand Univ Med Sci. 2006; 13(3): 9-15.
  19. Inic Z, Zegarac M, Inic M, Markovic I, Kozomara Z, Djurisic I, et al. Difference between Luminal A and Luminal B Subtypes According to Ki-67, Tumor Size, and Progesterone Receptor Negativity Providing Prognostic Information. Clinical Medicine Insights. Oncology. 2013; 8:107-11.
  20. Cheang MC, Chia SK, Voduc D, Gao D, Leung S, Snider J, et al. Ki67 index, HER2 status, and prognosis of patients with luminal B breast cancer. Journal of the National Cancer Institute. 2009; 101(10):736-50.
  21. Keam B, Im SA, Lee KH, Han SW, Oh DY, Kim JH, et al. Ki-67 can be used for further classification of triple negative breast cancer into two subtypes with different response and prognosis. Breast Cancer Research. 2011; 13(2):1-7.
  22. Feeley LP, Mulligan AM, Pinnaduwage D, Bull SB, Andrulis IL. Distinguishing luminal breast cancer subtypes by Ki67, progesterone receptor or TP53 status provides prognostic information. Modern Pathology. 2014; 27(4):554-61.
  23. Inwald EC, Klinkhammer-Schalke M, Hofstädter F, Zeman F, Koller M, 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 research and treatment. 2013; 139(2):539-52.
  24. Bonta I, Bonta D, Loch  MM, Eapen  A, Blanchard RA. Relationship of Ki67 to tumor size and lymph node metastasis in breast cancer. In ASCO Annual Meeting Proceedings 2012 May 20 (Vol. 30, No. 15_suppl, p. e21076).
  25. Keam B, Im SA, Lee KH, Han SW, Oh DY, Kim JH, et al. Ki-67 can be used for further classification of triple negative breast cancer into two subtypes with different response and prognosis. Breast Cancer Research. 2011; 13(2):1-7.
  26. Boyle P. Triple-negative breast cancer: epidemiological considerations and recommendations. Annals of Oncology. 2012; 23(suppl 6):vi7-12.
  27. Mirmalek SA, Hajilou M, Salimi Tabatabaee SA, Parsa Y, Yadollah-Damavandi S, et al. Prevalence of HER-2 and Hormone Receptors and P53 Mutations in the Pathologic Specimens of Breast Cancer Patients. International journal of breast cancer. 2014; 2014.
  28. Bonnefoi H, Litière S, Piccart M, MacGrogan G, Fumoleau P, Brain E, et al. Pathological complete response after neoadjuvant chemotherapy is an independent predictive factor irrespective of simplified breast cancer intrinsic subtypes: a landmark and two-step approach analyses from the EORTC 10994/BIG 1-00 phase III trial. Annals of oncology. 2014; 25(6):1128-36.
Iranian Journal of Pathology
Volume 13, Issue 1
Winter 2018
Pages 71-77

  • Receive Date 19 September 2016
  • Revise Date 29 January 2017
  • Accept Date 26 September 2017

Home

Guide for Authors

Submit Manuscript

Contact Us