Clinical significance of Ki-67 in neoadjuvant chemotherapy for primary breast cancer as a predictor for chemosensitivity and for prognosis

Breast Cancer. 2010 Oct;17(4):269-75. doi: 10.1007/s12282-009-0161-5.


Background: Neoadjuvant chemotherapy (NAC) is one of the main strategies for patients with locally advanced breast cancer. In recent years several biological markers such as estrogen receptor (ER), progesterone receptor (PgR), and HER2 were discovered to be predictive factors for the effectiveness of NAC to help individualize treatment. In this retrospective study, we focused on Ki-67 as a biological marker and examined the correlation between Ki-67 and chemosensitivity, and the prognosis after the start of treatment.

Patients and methods: Between July 1996 and March 2008, 148 patients with tumors ≥ 3 cm in diameter or lymph node metastases received NAC and surgery. The items investigated were ER/PgR and Ki-67 from core needle biopsy. The treatment regimens were EC in 36 cases, ET in 51 cases, and FEC-DOC in 61 cases. The patients with FEC-DOC regimen had smaller tumors and higher Ki-67 values than the others.

Results: Clinical response (cCR + cPR) was 79.7%, and the pathological complete response (pCR) was 14.2%. Multivariate analysis revealed that Ki-67 was significantly related to pCR. Moreover, there was no pathological responder in cases with Ki-67 < 25%. The Ki-67 values significantly decreased after NAC (median from 45.0 to 17.5%). Patients with cCR had significantly lower Ki-67 values after NAC than those with cPR, cSD, and cPD. There was a significant difference in the Ki-67 value in terms of the presence and the absence of recurrence (median 26.0% with recurrence vs. 12% without recurrence). The disease-free survival (DFS) rate after the start of treatment was significantly higher in the patients with Ki-67 < 12% after NAC than those with Ki-67 ≥ 12%.

Conclusion: The Ki-67 value before NAC was a significant predictive factor for the effectiveness of NAC. The Ki-67 values after NAC significantly decreased and correlated with clinical response and DFS. Therefore, higher Ki-67 values (≥ 25%) before NAC as well as lower values (<12%) after NAC might be clinically significant for treating patients.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Aromatase Inhibitors / administration & dosage
  • Biomarkers / metabolism
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Cell Proliferation / drug effects
  • Cyclophosphamide / administration & dosage
  • Docetaxel
  • Drug Resistance, Neoplasm
  • Epirubicin / administration & dosage
  • Etoposide / administration & dosage
  • Female
  • Fluorouracil / administration & dosage
  • Humans
  • Ki-67 Antigen / metabolism*
  • Logistic Models
  • Middle Aged
  • Multivariate Analysis
  • Neoadjuvant Therapy*
  • Prognosis
  • Receptor, ErbB-2 / metabolism
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism
  • Retrospective Studies
  • Survival Analysis
  • Tamoxifen / administration & dosage
  • Taxoids / administration & dosage
  • Tumor Suppressor Protein p53 / metabolism


  • Aromatase Inhibitors
  • Biomarkers
  • Ki-67 Antigen
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Taxoids
  • Tumor Suppressor Protein p53
  • Tamoxifen
  • Docetaxel
  • Epirubicin
  • Etoposide
  • Cyclophosphamide
  • Receptor, ErbB-2
  • Fluorouracil

Supplementary concepts

  • EC regimen
  • FEC protocol