Document Type : Short Communication


1 Breast Diseases Research Center, Cancer Institute, Tehran University of Medical Sciences, Tehran, Iran

2 Breast Diseases Research Center, Cancer Institute, Tehran University of Medical Sciences, Tehran, Iran Department of Surgery, Arash Women’s Hospital, Tehran University of Medical Sciences, Tehran, Iran

3 Mostafa Khomeini Hospital, Shahed University, Tehran, Iran

4 Department of Pathology, Cancer Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran



Background & Objective: Antigen Ki-67 (histone-based nuclear protein) is a static marker of tumor cell proliferation and growth and is commonly measured to indicate the effect of treatment in breast cancer patients. This single-arm trial study aimed to evaluate the effect of short-term endocrine therapy (letrozole) on Ki-67 levels in menopausal women with early hormone-positive breast cancer who were referred to two university hospitals.
Methods: Patients with a pre-treatment Ki67 of 5% or less were excluded from the study. Participants (n=25) received oral letrozole (2.5 mg daily) seven days before surgery. Ki-67% on both the biopsy and the surgical specimens were measured and compared.
Results and Conclusion: The mean age of patients was 62±9.4 (48-83 years). Our result indicated that consumption of letrozole before surgery for hormone-positive breast cancer can significantly decrease the level of Ki-67 (23.24±9.74 vs. 16.92±9.55, P=0.001 by paired t-test), with no drug-related adverse events.


Main Subjects

  1. Downs-Holmes C, Silverman P. Breast cancer: overview & updates. J Nurse Pract. 2011;36(12):20-6. [DOI:10.1097/01.NPR.0000407602.29522.d7] [PMID]
  2. Esposito A, Criscitiello C, Curigliano G. Highlights from the 14th St Gallen International Breast Cancer Conference 2015 in Vienna: Dealing with classification, prognostication, and prediction refinement to personalize the treatment of patients with early breast cancer. Ecancermedicalscience. 2015;9:518. [DOI:10.3332/ecancer.2015.518] [PMID]
  3. Cianfrocca M, Goldstein LJ. Prognostic and predictive factors in early-stage breast cancer. Oncologist. 2004;9(6):606-16. [DOI:10.1634/theoncologist.9-6-606] [PMID]
  4. Urruticoechea A, Smith IE, Dowsett M. Proliferation marker Ki-67 in early breast cancer. J Clin Oncol. 2005;23(28):7212-20. [DOI:10.1200/JCO.2005.07.501] [PMID]
  5. Li LT, Jiang G, Chen Q, Zheng JN. Ki67 is a promising molecular target in the diagnosis of cancer. Mol Med Rep. 2015;11(3):1566-72. [DOI:10.3892/mmr.2014.2914] [PMID]
  6. Faneyte IF, Schrama JG, Peterse JL, Remijnse PL, Rodenhuis S, Van de Vijver M. Breast cancer response to neoadjuvant chemotherapy: predictive markers and relation with outcome. Br J Cancer. 2003;88(3):406-12. [DOI:10.1038/sj.bjc.6600749] [PMID]
  7. Petit T, Wilt M, Velten M, Millon R, Rodier J-F, Borel C, et 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(2):205-11. [DOI:10.1016/S0959-8049(03)00675-0] [PMID]
  8. Pohl G, Rudas M, Taucher S, Stranzl T, Steger GG, Jakesz R, et al. Expression of cell cycle regulatory proteins in breast carcinomas before and after preoperative chemotherapy. Breast Cancer Res Treat. 2003;78:97-103. [DOI:10.1023/A:1022165715043] [PMID]
  9. Chang J, Ormerod M, Powles T, Allred D, Ashley S, Dowsett M. Apoptosis and proliferation as predictors of chemotherapy response in patients with breast carcinoma. Cancer. 2000;89(11):2145-52. [DOI:10.1002/1097-0142(20001201)89:113.0.CO;2-S] [PMID]
  10. Harper-Wynne CL, Sacks NP, Shenton K, MacNeill FA, Sauven P, Laidlaw IJ, et al. Comparison of the systemic and intratumoral effects of tamoxifen and the aromatase inhibitor vorozole in postmenopausal patients with primary breast cancer. J Clin Oncol. 2002;20(4):1026-35. [DOI:10.1200/JCO.2002.20.4.1026] [PMID]
  11. Makris A, Powles T, Allred D, Ashley S, Ormerod M, Titley J, et al. Changes in hormone receptors and proliferation markers in tamoxifen treated breast cancer patients and the relationship with response. Breast Cancer Res Treat. 1998;48:11-20. [DOI:10.1023/A:1005973529921] [PMID]
  12. Dowsett M, Smith IE, Ebbs SR, Dixon JM, Skene A, Griffith C, 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(2):951s-8s. [DOI:10.1158/1078-0432.951s.11.2]
  13. Spring LM, Gupta A, Reynolds KL, Gadd MA, Ellisen LW, Isakoff SJ, et al. Neoadjuvant endocrine therapy for estrogen receptor-positive breast cancer: a systematic review and meta-analysis. JAMA Oncol. 2016;2(11):1477-86. [DOI:10.1001/jamaoncol.2016.1897] [PMID]
  14. Chlebowski RT, Geller ML. Adherence to endocrine therapy for breast cancer. Oncol. 2007;71(1-2):1-9. [DOI:10.1159/000100444] [PMID]
  15. Iwamoto T, Katagiri T, Niikura N, Miyoshi Y, Kochi M, Nogami T, et al. Immunohistochemical Ki67 after short-term hormone therapy identifies low-risk breast cancers as reliably as genomic markers. Oncotarget. 2017;8(16):26122. [DOI:10.18632/oncotarget.15385] [PMID]
  16. Cohen AL, Factor RE, Mooney K, Salama ME, Wade M, Serpico V, et al. POWERPIINC (PreOperative Window of Endocrine TheRapy Provides Information to Increase Compliance) trial: Changes in tumor proliferation index and quality of life with 7 days of preoperative tamoxifen. Breast. 2017;31:219-23. [DOI:10.1016/j.breast.2016.11.016] [PMID]
  17. 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. J Natl Cancer Inst. 2007;99(2):167-70. [DOI:10.1093/jnci/djk020] [PMID]
  18. Tsoi DT, Inoue M, Kelly CM, Verma S, Pritchard KI. Cost-effectiveness analysis of recurrence score-guided treatment using a 21-gene assay in early breast cancer. Oncologist. 2010;15(5):457-65. [DOI:10.1634/theoncologist.2009-0275] [PMID]
  19. Kondo M, Hoshi S-L, Yamanaka T, Ishiguro H, Toi M. Economic evaluation of the 21-gene signature (Onco type DX®) in lymph node-negative/positive, hormone receptor-positive early-stage breast cancer based on Japanese validation study (JBCRG-TR03). Breast Cancer Res Treat. 2011;127:739-49. [DOI:10.1007/s10549-010-1243-y] [PMID]

20. DeFriend DJ, Howell A, Nicholson RI, Anderson E, Dowsett M, Mansel RE, et al. Investigation of a new pure antiestrogen (ICI 182780) in women with primary breast cancer. Cancer Res. 1994;54(2):408-14.