Correlation of Preoperative Ki67 and Serum CA15.3 Levels with Outcome in Early Breast Cancers - a Multi Institutional Study

  • Rasmy, A (Medical Oncology Department, Zagazig University) ;
  • Abozeed, W (Clinical Oncology Department, Faculty of Medicine, Mansoura University) ;
  • Elsamany, S (Medical Oncology Department, Oncology Centre, Mansoura University) ;
  • El Baiomy, M (Medical Oncology Department, Oncology Centre, Mansoura University) ;
  • Nashwa, A (Medical Oncology Unit, King Khaled University Hospital, King Saud University) ;
  • Amrallah, A (Medical Oncology Department, Zagazig University) ;
  • Hasaan, E (Adult Oncology Department, Oncology Center, King Fahad Specialist Hospital) ;
  • Alzahrani, A (King Abdullah Medical City) ;
  • Faris, M (Adult Oncology Department, Oncology Center, King Fahad Specialist Hospital) ;
  • Alsaleh, K (Medical Oncology Unit, King Khaled University Hospital, King Saud University) ;
  • AlFaraj, A (Medical Oncology Unit, King Khaled University Hospital, King Saud University)
  • Published : 2016.07.01


Background: To investigate the association between preoperative pathological Ki-67 labeling index and serum tumor marker cancer antigen 15-3 (CA 15-3) with clinic-pathological parameters and treatment outcomes in early breast cancer. Materials and Methods: A retrospective study at 4 cancer centers in Saudi Arabia and Egypt was performed. Data were collected for female patients diagnosed with unilateral early breast cancer between March 2010 and October 2013. Cases treated with neoadjuvant chemotherapy (NACT) followed by surgery and radiotherapy were included. NACT included 6-8 cycles of anthracycline and taxane based regimens. Trastuzumab and hormonal treatments were added according to HER2 and hormone receptor status. Baseline serum CA15.3 and pathological Ki67 levels were evaluated and correlated with disease free survival (DFS) and overall survival (OS). Results: A total of 280 pts was included. The median age was 49 years (38-66 y) and median overall survival was 35 (20-38) months (mo). Estrogen receptors (ER), progesterone receptors (PR) and HER 2 receptors were positive in 233 (83.2%), 198 (70%) and 65 cases (23.2%), respectively. High preoperative Ki67 and CA15.3 were noted in 177 (63.2%) and 131 (46.8%). A total of 45 (16%) patients had distal or local recurrence and 24 (8.6%) died of their disease. Most of the relapsed cases had high preoperative Ki-67 (n=41, 91%) and CA15.3 (n=28, 62%) values. All of the patients who died had a high Ki-67 but CA15.3 was high in 9 (37%) only. Mean DFS/OS in patients with high preoperative Ki-67 was 32 months /32 months as compared to 37 months/35 months in those with normal Ki-67 (p<0.001). Correlation of preoperative CA15.3 and survival was statistically not significant. Conclusions:Preoperative Ki-67 can be a predictive and prognostic marker. Higher levels are associated with poor DFS and OS in patients with early BC.


  1. Canizares F, Sola J, Perez M, et al (2001). Preoperative values of CA 15-3 and CEA as prognostic factors in breast cancer: a multivariate analysis. Tumor Biol, 22, 273-281.
  2. Chu W, and Ryu D, (2016). Clinical significance of serum CA15-3 as a prognostic parameter during follow-up periods in patients with breast cancer. Ann Surg Treat Res, 90, 57-63.
  3. Coleman M, Quaresma M, Berrino F, et al (2008). Cancer survival in five continents: A worldwide population-based study (CONCORD). Lancet Oncol, 9, 730-56.
  4. Colozza M, Azambuja E, Cardoso F, et al (2005). Proliferative markers as prognostic and predictive tools in early breast cancer: where are we now? Ann Oncol, 16, 1723-39.
  5. De Azambuja E, Cardoso F, de Castro G, et al (2007). Ki-67 as prognostic marker in early breast cancer: a meta-analysis of published studies involving 12,155 patients. Br J Cancer, 96, 1504-13.
  6. DeVita, Hellman and Rosenberg's Cancer (2014). Principles & Practice of Oncology, 10th edition, 1632.
  7. Duffy M, Duggan C, Keane R, et al (2004). High preoperative CA 15-3 concentrations predict adverse outcome in nodenegative and node-positive breast cancer: study of 600 patients with histologically confirmed breast cancer. Clin Chem, 50, 559-63.
  8. Fotinos-Ioannis D, Anastasia K, Anna G, et al (2015). Early-Stage breast cancer in the elderly: confronting an old clinical problem. J Breast Cancer, 18, 207-17.
  9. Gasparini G, Toi M, Gion M, et al (1997). Prognostic significance of vascular endothelial growth factor protein in nodenegative breast carcinoma. J Natl Cancer Inst, 89, 139-47.
  10. Gasparini G, (1998). Prognostic variables in node-negative and node-positive breast cancer. Breast Cancer Res Treat, 52, 321-31.
  11. Gnant M, Harbeck N, Thomssen C (2011). St. Gallen summary of the Consensus Discussion. Breast Care, 6, 136-41.
  12. Hashim Z, (2014). The significance of CA15-3 in breast cancer patients and its relationship to HER-2 receptor status. Int J Immunopathol Pharmacol, 27, 45-51.
  13. Jones RL, Salter J, A'Hern R, et al (2009). The prognostic significance of Ki67 before and after neoadjuvant chemotherapy in breast cancer. Breast Cancer Res Treat, 116, 53-68.
  14. Kobayashi T, Iwaya K, Moriya T, et al (2013). A simple immunohistochemical panel comprising 2 conventional markers, Ki67 and p53, is a powerful tool for predicting patient outcome in luminal-type breast cancer. BMC Clin Pathol, 6, 13-5.
  15. Kurebayashi J, Kanomata N, Shimo T, et al (2014). Marked lymphovascular invasion, progesterone receptor negativity, and high Ki67 labeling index predict poor outcome in breast cancer patients treated with endocrine therapy alone. Breast Cancer, 21, 214-22.
  16. Molina R, Filella X, Alicarte J, et al (2003). Prospective evaluation of CEA and CA 15.3 in patients with locoregional breast cancer. Anticancer Res, 23, 1035-41.
  17. Molina R, Jo J, Filella X, et al (1998). c-erbB-2 oncoprotein, CEA, and CA 15.3 in patients with breast cancer: prognostic value. Breast Cancer Res Treat, 51, 109-19.
  18. Sandri M, Salvatici M, Botteri E, et al (2015). Prognostic role of CA15.3 in 7942 patients with operable breast cancer. Breast Cancer Res Treat, 132, 317-26.
  19. Shao Y, Sun X, He Y, et al (2015). Elevated levels of serum tumor markers CEA and CA15-3 are prognostic parameters for different molecular subtypes of breast cancer. PLoS ONE, 10, 133830.
  20. Sokoll L, Chan D (2004). Clinical chemistry: Tumor markers. In: Abeloff MD, Armitage JO, Niederhuber JE,Kastan MB, McKenna WG, editors. In Abeloff Clinical Oncology. 3rd ed. Pennsylvania: Elsevier Churchill Livingston.
  21. Stuart-Harris R, Caldas C, Pinder S, et al (2008). Proliferation markers and survival in early breast cancer: a systematic review and meta-analysis of 85 studies in 32, 825 patients. Breast, 17, 323-34.
  22. Tampellini M, Berruti A, Gerbino A, et al (1997). The relationship between CA 15-3 serum levels and disease extent in predicting overall survival of breast cancer patients with newly diagnosed metastatic disease. Br J Cancer, 75, 698-702.
  23. Tanei T, Shimomura A, Shimazu K, et al (2011). Prognostic significance of Ki67 index after neoadjuvant chemotherapy in breast cancer. Eur J Surg Oncol, 37, 155-61.
  24. Waxman J (1995). Tumor markers. Quart J Med, 88, 233-41.
  25. Yerushalmi R, Woods R, Ravdin P, et al (2010). Ki67 in breast cancer:prognostic and predictive potential. Lancet Oncol, 11, 174-83.