Breast Cancer Research and Treatment

, Volume 178, Issue 2, pp 327–335 | Cite as

A randomized, double-blind, window of opportunity trial evaluating the effects of chloroquine in breast cancer patients

  • Angel Arnaout
  • Susan J. Robertson
  • Gregory R. Pond
  • Hoyun Lee
  • Ahwon Jeong
  • Luisa Ianni
  • Lynne Kroeger
  • John Hilton
  • Stuart Coupland
  • Chloe Gottlieb
  • Bernard Hurley
  • Anne McCarthy
  • Mark ClemonsEmail author
Clinical trial



Chloroquine has demonstrated anti-tumor activities through autophagy inhibition and cell cycle disruption. This study aimed to assess the effect of single-agent chloroquine on breast tumor cellular proliferation in a randomized, phase II, double-blind, placebo-controlled, pre-surgical window of opportunity trial.


Patients with newly diagnosed breast cancer were randomized 2:1 to chloroquine 500 mg daily or placebo for 2- to 6-weeks prior to their breast surgery. The primary outcome was the relative change in measures of proliferation (Ki67) in primary breast cancer cells pre- and post-treatment. Adverse events and toxicity profiles were also evaluated.


From September 2015 to December 2016, 70 patients were randomized [46 (66%) chloroquine and 24 (34%) placebo]. Ten patients who were randomized to chloroquine withdrew from study due to adverse events. Mean duration of drug intake was 15 days (range 14–29 days). There were no significant differences between the chloroquine or placebo arms with respect to either the percentage change (− 0.4 vs. − 1.2, p = 0.088) or absolute change (− 2.0% vs. − 5.2%, p = 0.066) in Ki67 index pre- and post-drug treatment. Although adverse effects were minimal and all classified as grade 1, the effects were significant enough to cause nearly 15% of patients to discontinue therapy.


Treatment with single-agent chloroquine 500 mg daily in the preoperative setting was not associated with any significant effects on breast cancer cellular proliferation. It was, however, associated with toxicity that may affect its broader use in oncology.


Window of opportunity clinical trial Chloroquine Breast cancer 



The authors are grateful to the research staff for their assistance in recruiting participants and for data collection.


This trial was supported by the Canadian Breast Cancer Foundation Ontario Chapter and University of Ottawa Department of Surgery research Grant.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee (Ottawa Hospital Research Ethics Board) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

10549_2019_5381_MOESM1_ESM.pdf (35 kb)
Supplementary material 1 (PDF 35 kb)


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Copyright information

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

Authors and Affiliations

  • Angel Arnaout
    • 1
    • 2
    • 3
  • Susan J. Robertson
    • 4
  • Gregory R. Pond
    • 5
  • Hoyun Lee
    • 6
    • 7
  • Ahwon Jeong
    • 2
  • Luisa Ianni
    • 2
    • 8
  • Lynne Kroeger
    • 8
  • John Hilton
    • 2
    • 3
    • 9
  • Stuart Coupland
    • 10
  • Chloe Gottlieb
    • 10
  • Bernard Hurley
    • 10
  • Anne McCarthy
    • 11
  • Mark Clemons
    • 2
    • 3
    • 9
    Email author
  1. 1.Division of Surgical Oncology, Department of SurgeryOttawa HospitalOttawaCanada
  2. 2.Cancer Therapeutics ProgramOttawa Hospital Research InstituteOttawaCanada
  3. 3.Clinical Epidemiology ProgramOttawa Hospital Research InstituteOttawaCanada
  4. 4.Division of Anatomical PathologyOttawa HospitalOttawaCanada
  5. 5.Department of OncologyMcMaster UniversityHamiltonCanada
  6. 6.Health Sciences North Research InstituteSudburyCanada
  7. 7.Department of MedicineUniversity of OttawaOttawaCanada
  8. 8.Ottawa Hospital Breast Health CentreOttawaCanada
  9. 9.Division of Medical Oncology, Department of MedicineUniversity of Ottawa and Ottawa Hospital Cancer Center, The Ottawa Hospital Cancer CentreOttawaCanada
  10. 10.Department of OphthalmologyUniversity of OttawaOttawaCanada
  11. 11.Division of Infectious Diseases, Department of MedicineOttawa HospitalOttawaCanada

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