Goodwin, Pamela J.; Ennis, Marguerite; Pritchard, Kathleen I.; Koo, Jarley; Hood, Nicky

1. Vitamin D Deficiency is Common at Breast Cancer Diagnosis and is Associated with a Significantly Higher Riskof Distant Recurrence and Death in a Prospective Cohort Study of T1-3, N0-1, M0 Breast Cancer Goodwin, Pamela J.; Ennis, Marguerite; Pritchard, Kathleen I.; Koo, Jarley; Hood, Nicky Samuel Lunenfeld Research Institute at Mount Sinai Hospital, Sunnybrook Health Sciences Center and St. Michael’s Hospital, University of Toronto Funded by the Breast Cancer Research Foundation

2. Vitamin D Deficiency in Breast Cancer Metabolism Ingraham B et al. Curr Med Res Opin 2006

3. Vitamin D Deficiency in Breast Cancer Objectives In a cohort of women with newly diagnosed breast cancer: • To determine the frequency of vitamin D deficiency • To identify factors (patient, tumor) associated with vitamin D deficiency • To determine associations of vitamin D deficiency with distant disease-free survival and overall survival • To explore factors (patient, tumor) that modify the association of vitamin D with distant disease-free survival and overall survival

4. Vitamin D Deficiency in Breast Cancer • Locoregional Breast Cancer T1-3, N0-1, M0 • Dx 1989 to 1996 (Toronto - latitude 43 40) • n = 512 women, mean age 50.1 years * Analysed for 25-OH vitamin D in 2007 (RIA Diasorin – Stillwater, Minnesota) • Blood: frozen at -80C * • Diet, Physical Activity, Clinical Data Systemic Treatment (if any) • Annual Follow-up to 2007 • distant recurrence • death • Mean 11.6 years

5. Vitamin D Deficiency in Breast Cancer 25-OH Vitamin D Levels at Diagnosis (Toronto – latitude 43 40) Mean: 58.1 ± 23.4 nmol/L Range: 8-177 nmol/L

6. Vitamin D Deficiency in Breast Cancer Tumor and Treatment Related Factors Associated with Vitamin D

7. 1.0 Sufficient 0.8 Insufficient Deficient 0.6 Proportion distant disease free 0.4 0.2 0.0 0 2 4 6 8 10 12 Years since diagnosis Vitamin D Deficiency in Breast Cancer Distant Disease-Free Survival p=0.02

8. 1.0 Sufficient Insufficient 0.8 Deficient 0.6 Proportion survived 0.4 0.2 0.0 0 2 4 6 8 10 12 Years since diagnosis Vitamin D Deficiency in Breast Cancer Overall Survival p=0.02

9. 2 1 Log hazard of death 0 -1 50 100 150 25-Hydroxyvitamin D (nmol/L) Vitamin D Deficiency in Breast Cancer Overall Survival Smoothed Log Hazard

10. Vitamin D Deficiency in Breast Cancer Conclusions • Vitamin D deficiency/insufficiency was common at breast cancer diagnosis. Only 24% had levels considered sufficient. • Vitamin D deficiency was associated with higher grade tumors. • Vitamin D deficiency was associated with an increased risk of distant recurrence and death. • Replication is recommended; an RCT of vitamin D supplementation may be indicated if results are replicated. • Caution is recommended in applying these results in the clinical situation – it is premature to advise breast cancer patients to use vitamin D supplementation in doses higher than recommended for bone health. Consideration should be given to measuring vitamin D levels in blood to ensure they are in a healthy range.

11. Natural History of the Disease ASCO 2008 Take Home Messages for Clinical Practice ! VITAMIN D ! There is “nothing to lose” in measuring/correcting vitamin D levels at BC diagnosis