Breast Cancer Research and Treatment

, Volume 147, Issue 2, pp 407–414 | Cite as

Ki67 measured in metastatic tissue and prognosis in patients with advanced breast cancer

  • Claudette Falato
  • Julie Lorent
  • Edneia Tani
  • Eva Karlsson
  • Paul K. Wright
  • Jonas Bergh
  • Theodoros Foukakis


The purpose of this study is to determine the prognostic role of Ki67 evaluated in relapse biopsies from patients with metastatic breast cancer (MBC). Two hundred and ten patients diagnosed with MBC in Stockholm, Sweden between 1998 and 2009 and with Ki67 assessed at time of first systemic relapse (mKi67) were retrospectively identified and divided into two groups according to mKi67 fraction (low ≤20 %, high >20 %). Post-relapse survival was compared between the groups using Kaplan–Meier and Cox regression methods. Death rate as function of continuous mKi67 was also evaluated. Furthermore, the prognostic role of intra-individual change in Ki67 between primary tumor and matched metastasis was explored by Kaplan–Meier plots. One hundred and twenty-five patients had low and 85 had high mKi67. Median survival was 25 and 17 months in low- and high-mKi67 group, respectively [hazard ratio (HR) 0.69, 95 % confidence intervals (CI) 0.51–0.92, P = 0.01]. In a multivariate model adjusted for prognostic confounders, low-mKi67 showed a non-significant trend toward better survival (HR 0.85, 95 %CI 0.62–1.16, P = 0.30). Nevertheless, mKi67 independently correlated with survival when compared with primary tumor proliferation (HR 0.56, 95 %CI 0.38–0.81, P = 0.002). The 2-year death rate steeply increased as mKi67 increased. Moreover, the change from high in primary tumor to low in metastasis significantly correlated with longer survival when compared with stable Ki67 levels (HR 0.48, 95 %CI 0.31–0.76, P = 0.002). In this cohort of MBC patients, mKi67 inversely but not independently correlated with survival. However, a significant association between mKi67 and survival was shown regardless of primary tumor proliferation.


Metastatic breast cancer Prognosis Proliferation Ki67 Relapse biopsy 



Confidence intervals


Early breast cancer


Estrogen receptor


Fine-needle aspiration cytology


Human epidermal growth factor receptor 2


Hazard ratio


Metastatic breast cancer


Ki67 measured in metastasis


Overall survival


Ki67 measured in primary tumor


Progesterone receptor


Recurrence-free interval


Tissue microarray sections



We would like to thank Dr. Ulla Wilking for her help in data collection. This Research Project was supported by the European Society of Medical Oncology (ESMO) “Translational Research Fellowship” to Dr. Falato, the “Umberto Veronesi” Foundation, the Breast Cancer Theme Center (BRECT) at Karolinska Institutet, the Swedish Cancer Foundation, the Cancer Society in Stockholm, the Swedish Research Council, and the Stockholm County Council. Any views, opinions, findings, conclusions, or recommendations expressed in this material are those solely of the authors and do not necessarily reflect those of the above-mentioned organizations.

Conflict of interests

The authors declare that they have no competing interests.

Supplementary material

10549_2014_3096_MOESM1_ESM.pdf (45 kb)
Supplementary material 1 (PDF 45 kb)
10549_2014_3096_MOESM2_ESM.pdf (46 kb)
Supplementary material 2 (PDF 45 kb)
10549_2014_3096_MOESM3_ESM.pdf (322 kb)
Supplementary material 3 (PDF 321 kb)
10549_2014_3096_MOESM4_ESM.pdf (66 kb)
Supplementary material 4 (PDF 65 kb)


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Claudette Falato
    • 1
  • Julie Lorent
    • 1
  • Edneia Tani
    • 1
    • 3
  • Eva Karlsson
    • 1
  • Paul K. Wright
    • 2
  • Jonas Bergh
    • 1
    • 3
  • Theodoros Foukakis
    • 1
    • 3
  1. 1.Department of Oncology and PathologyKarolinska InstitutetStockholmSweden
  2. 2.Department of Histopathology and Cytopathology, Manchester Royal InfirmaryCentral Manchester University Hospitals NHS Foundation TrustManchesterUK
  3. 3.Department of Oncology and PathologyCCK, R8:03, Karolinska University HospitalStockholmSweden

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