Randomized window of opportunity trial evaluating high-dose vitamin D in breast cancer patients



Epidemiologic and preclinical data suggest a potential role for vitamin D in breast cancer treatment and prevention. However, results of prospective randomized trials are inconsistent. The objective of this study was to assess the effects of high-dose cholecalciferol (vitamin D3) on breast tumour proliferation and apoptosis.


We conducted a prospective, randomized, phase 2, double-blinded pre-surgical window of opportunity trial. Newly diagnosed breast cancer patients were randomized to receive 40,000 IU of vitamin D3 per day or placebo for 2 to 6 weeks prior to breast surgery. The primary outcome was the relative change in proliferation (Ki67) and apoptosis (cleaved caspase 3 apoptotic assay [CC3]) in primary breast cancer cells pre and post treatment.


Of 83 patients randomized, 80 completed the study (43 (53.8%) vitamin D and 37 (46.3%) placebo). Mean duration of drug intake was 19 days (range 9–28 days). There were no significant differences between the control arm and the vitamin D arm in percent changes of either Ki67 index (1.6% vs. 16.7%, p = 0.25) or CC3 (− 55.9% vs. − 45.9%, p = 0.28). Serum 25-hydroxyvitamin D (25-OHD) levels were 3 times higher in the vitamin D arm (62 nmol/L vs. 246 nmol/L, p < 0.001). Adverse effects were minimal and all classified as grade 1.


Despite significantly higher levels of serum 25-OHD in the vitamin D-treated group, this was not associated with any significant effects on tumour proliferation or apoptosis. These findings are consistent with the lack of benefit observed in prospective prevention trials.

Trial registry

Trial registration clinicaltrials.gov NCT01948128.

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The primary investigator developed the protocol during 14th Annual Joint ECCO-AACR-EORTC-ESMO Flims “Methods in Clinical Cancer Research” Workshop 2012. The authors are grateful to the research staff for their assistance in recruiting participants and for data collection.


This work was supported by the Canadian Breast Cancer Foundation and University of Ottawa Department of Surgery research grant.

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Correspondence to Mark Clemons.

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Conflict of interest

Dr Vieth is an unpaid advisor to the Vitamin D Society, and receives royalties from partial ownership and a patent pertaining to vitamin D supplementation.

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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.

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

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Arnaout, A., Robertson, S., Pond, G.R. et al. Randomized window of opportunity trial evaluating high-dose vitamin D in breast cancer patients. Breast Cancer Res Treat 178, 347–356 (2019). https://doi.org/10.1007/s10549-019-05392-9

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  • Vitamin D
  • Window of opportunity
  • Clinical trial
  • Breast cancer