PMID- 31399931
OWN - NLM
STAT- MEDLINE
DCOM- 20200226
LR  - 20200226
IS  - 1573-7217 (Electronic)
IS  - 0167-6806 (Linking)
VI  - 178
IP  - 2
DP  - 2019 Nov
TI  - Randomized window of opportunity trial evaluating high-dose vitamin D in breast 
      cancer patients.
PG  - 347-356
LID - 10.1007/s10549-019-05392-9 [doi]
AB  - PURPOSE: 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. METHODS: 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. 
      RESULTS: 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. CONCLUSIONS: 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.
FAU - Arnaout, Angel
AU  - Arnaout A
AD  - Division of Surgical Oncology, Department of Surgery, Ottawa Hospital, Ottawa, 
      Canada.
AD  - Cancer Therapeutics Program, Ottawa Hospital Research Institute, Ottawa, Canada.
FAU - Robertson, Susan
AU  - Robertson S
AD  - Division of Anatomical Pathology, Ottawa Hospital, Ottawa, Canada.
FAU - Pond, Gregory R
AU  - Pond GR
AD  - Department of Oncology, McMaster University, Hamilton, Canada.
FAU - Vieth, Reinhold
AU  - Vieth R
AD  - Department of Laboratory Medicine and Pathobiology, University of Toronto, 
      Toronto, Canada.
FAU - Jeong, Ahwon
AU  - Jeong A
AD  - Cancer Therapeutics Program, Ottawa Hospital Research Institute, Ottawa, Canada.
FAU - Hilton, John
AU  - Hilton J
AD  - Cancer Therapeutics Program, Ottawa Hospital Research Institute, Ottawa, Canada.
AD  - Division of Medical Oncology, Department of Medicine, University of Ottawa and 
      Ottawa Hospital Cancer Center, Ottawa, ON, Canada.
FAU - Ramsey, Timothy
AU  - Ramsey T
AD  - Center for Practice Changing Research, Ottawa Hospital Research Institute, 
      Ottawa, Canada.
FAU - Clemons, Mark
AU  - Clemons M
AUID- ORCID: 0000-0002-0738-2713
AD  - Cancer Therapeutics Program, Ottawa Hospital Research Institute, Ottawa, Canada. 
      mclemons@toh.ca.
AD  - Division of Medical Oncology, Department of Medicine, University of Ottawa and 
      Ottawa Hospital Cancer Center, Ottawa, ON, Canada. mclemons@toh.ca.
LA  - eng
SI  - ClinicalTrials.gov/NCT01948128
GR  - CBCF/Canadian Cancer Society/
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20190809
PL  - Netherlands
TA  - Breast Cancer Res Treat
JT  - Breast cancer research and treatment
JID - 8111104
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Biomarkers)
RN  - 0 (Ki-67 Antigen)
RN  - 0 (MKI67 protein, human)
RN  - 1406-16-2 (Vitamin D)
RN  - EC 3.4.22.- (Caspase 3)
SB  - IM
MH  - Antineoplastic Agents/*administration & dosage
MH  - Apoptosis
MH  - Biomarkers
MH  - Breast Neoplasms/diagnosis/*drug therapy/mortality/surgery
MH  - Caspase 3/metabolism
MH  - Female
MH  - Humans
MH  - Ki-67 Antigen/metabolism
MH  - Male
MH  - Neoplasm Grading
MH  - Neoplasm Staging
MH  - Preoperative Care
MH  - Treatment Outcome
MH  - Vitamin D/*administration & dosage
OTO - NOTNLM
OT  - Breast cancer
OT  - Clinical trial
OT  - Vitamin D
OT  - Window of opportunity
EDAT- 2019/08/11 06:00
MHDA- 2020/02/27 06:00
CRDT- 2019/08/11 06:00
PHST- 2019/07/08 00:00 [received]
PHST- 2019/08/02 00:00 [accepted]
PHST- 2019/08/11 06:00 [pubmed]
PHST- 2020/02/27 06:00 [medline]
PHST- 2019/08/11 06:00 [entrez]
AID - 10.1007/s10549-019-05392-9 [pii]
AID - 10.1007/s10549-019-05392-9 [doi]
PST - ppublish
SO  - Breast Cancer Res Treat. 2019 Nov;178(2):347-356. doi: 
      10.1007/s10549-019-05392-9. Epub 2019 Aug 9.