Prognostic effect of Ki-67 in common clinical subgroups of patients with HER2-negative, hormone receptor-positive early breast cancer

  • Peter A. FaschingEmail author
  • Paul Gass
  • Lothar Häberle
  • Bernhard Volz
  • Alexander Hein
  • Carolin C. Hack
  • Michael P. Lux
  • Sebastian M. Jud
  • Arndt Hartmann
  • Matthias W. Beckmann
  • Dennis J. Slamon
  • Ramona Erber
Clinical Trial



Several clinical trials have investigated the prognostic and predictive usefulness of molecular markers. With limited predictive value, molecular markers have mainly been used to identify prognostic subgroups in which the indication for chemotherapy is doubtful and the prognosis is favorable enough for chemotherapy to be avoided. However, limited information is available about which groups of patients may benefit from additional therapy. This study aimed to describe the prognostic effects of Ki-67 in several common subgroups of patients with early breast cancer.


This retrospective study analyzed a single-center cohort of 3140 patients with HER2−, hormone receptor-positive breast cancer. Five-year disease-free survival (DFS) rates were calculated for low (< 10%), intermediate (10–19%), and high (≥ 20%) Ki-67 expression levels, as assessed by immunohistochemistry, and for subgroups relative to age, body mass index, disease stage, tumor grade, and (neo-)adjuvant chemotherapy. It was also investigated whether Ki-67 had different effects on DFS in these subgroups.


The 5-year DFS rates for patients with low, intermediate, and high levels of Ki-67 expression were 0.90, 0.89, and 0.77, respectively. Ki-67 was able to further differentiate patients with an intermediate prognosis into different prognostic groups relative to common clinical parameters. Patients with stage II breast cancer had 5-year DFS rates of 0.84, 0.88, and 0.79 for low, intermediate, and high levels of Ki-67 expression. Ki-67 had different prognostic effects in subgroups defined by age and tumor grade.


Ki-67 may help identify patients in intermediate prognostic groups with an unfavorable prognosis who may benefit from further therapy.


Breast cancer Ki-67 Proliferation Molecular marker Prognosis 


Compliance with ethical standards

Conflict of interest

AH has received honoraria from Roche, Janssen, Merck Sharp Dome, AstraZeneca, Novartis, Cepheid, Abbvie and Boehringer-Ingelheim. His institution performs research with Grants from Biontech, Janssen, Cepheid, Roche and Qiagen. DJS has received honoraria from Novartis, Pfizer and Lilly and owns stock in Pfizer, Amgen and Seattle Genetics. His institution performs research with Grants from Novartis. PAF has received honoraria from Novartis, Amgen, Pfizer, Roche, Teva, Celgene, Eisai, Daiichi-Sankyo and PUMA. His institution performs research with Grants from Biontech and Novartis. PG has received honoraria from Novartis, travel support from Novartis, Roche and PharmaMar. MPL has received honoraria from Novartis, AstraZeneca, Roche, Pfizer, Lilly Eisai, Genomic Health and Tesaro. The remaining authors declare that they have no conflict of interest.

Ethical approval

Approval for this retrospective study was obtained from the Ethics Committee of the Faculty of Medicine at Friedrich Alexander University of Erlangen-Nuremberg. All procedures were in accordance with the Ethical Standards of the Institutional and/or National Research Committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from each individual participant included in the study.

Supplementary material

10549_2019_5198_MOESM1_ESM.docx (5 mb)
Supplementary material 1 (DOCX 5131 KB)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Peter A. Fasching
    • 1
    • 2
    Email author
  • Paul Gass
    • 1
  • Lothar Häberle
    • 1
    • 3
  • Bernhard Volz
    • 1
  • Alexander Hein
    • 1
  • Carolin C. Hack
    • 1
  • Michael P. Lux
    • 1
  • Sebastian M. Jud
    • 1
  • Arndt Hartmann
    • 4
  • Matthias W. Beckmann
    • 1
  • Dennis J. Slamon
    • 2
  • Ramona Erber
    • 4
  1. 1.Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, Erlangen University HospitalFriedrich Alexander University of Erlangen-NurembergNurembergGermany
  2. 2.Division of Hematology/Oncology, Department of Medicine, David Geffen School of MedicineUniversity of California at Los AngelesLos AngelesUSA
  3. 3.Biostatistics Unit, Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, Erlangen University HospitalFriedrich Alexander University of Erlangen-NurembergNurembergGermany
  4. 4.Comprehensive Cancer Center Erlangen-EMN, Institute of Pathology, Erlangen University HospitalFriedrich Alexander University of Erlangen-NurembergNurembergGermany

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