Angel Arnaout1,2, Susan Robertson3, Gregory R Pond4, Reinhold Vieth5, Ahwon Jeong2, John Hilton2,6, Timothy Ramsey7, Mark Clemons8,9. 1. Division of Surgical Oncology, Department of Surgery, Ottawa Hospital, Ottawa, Canada. 2. Cancer Therapeutics Program, Ottawa Hospital Research Institute, Ottawa, Canada. 3. Division of Anatomical Pathology, Ottawa Hospital, Ottawa, Canada. 4. Department of Oncology, McMaster University, Hamilton, Canada. 5. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada. 6. Division of Medical Oncology, Department of Medicine, University of Ottawa and Ottawa Hospital Cancer Center, Ottawa, ON, Canada. 7. Center for Practice Changing Research, Ottawa Hospital Research Institute, Ottawa, Canada. 8. Cancer Therapeutics Program, Ottawa Hospital Research Institute, Ottawa, Canada. mclemons@toh.ca. 9. Division of Medical Oncology, Department of Medicine, University of Ottawa and Ottawa Hospital Cancer Center, Ottawa, ON, Canada. mclemons@toh.ca.
Abstract
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.
RCT Entities:
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 cancerpatients 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.
Entities:
Keywords:
Breast cancer; Clinical trial; Vitamin D; Window of opportunity
Authors: Carmen Griñan-Lison; Jose L Blaya-Cánovas; Araceli López-Tejada; Marta Ávalos-Moreno; Alba Navarro-Ocón; Francisca E Cara; Adrián González-González; Jose A Lorente; Juan A Marchal; Sergio Granados-Principal Journal: Antioxidants (Basel) Date: 2021-01-31
Authors: Torsten O Nielsen; Samuel C Y Leung; David L Rimm; Andrew Dodson; Balazs Acs; Sunil Badve; Carsten Denkert; Matthew J Ellis; Susan Fineberg; Margaret Flowers; Hans H Kreipe; Anne-Vibeke Laenkholm; Hongchao Pan; Frédérique M Penault-Llorca; Mei-Yin Polley; Roberto Salgado; Ian E Smith; Tomoharu Sugie; John M S Bartlett; Lisa M McShane; Mitch Dowsett; Daniel F Hayes Journal: J Natl Cancer Inst Date: 2021-07-01 Impact factor: 13.506