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Vitamin D Deficiency is Common at Breast Cancer Diagnosis
and is Associated with a Significantly Higher Risk
of 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
Vitamin D Deficiency in Breast Cancer
Metabolism
Ingraham B et al. Curr Med Res Opin 2006
Vitamin D Deficiency in Breast Cancer
Objectives
In a cohort of women with newly diagnosed breast cancer:
1. To determine the frequency of vitamin D deficiency
2. To identify factors (patient, tumor) associated with
vitamin D deficiency
3. To determine associations of vitamin D deficiency with
distant disease-free survival and overall survival
4. To explore factors (patient, tumor) that modify the
association of vitamin D with distant disease-free
survival and overall survival
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
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
* Analysed for 25-OH vitamin D in 2007 (RIA Diasorin – Stillwater, Minnesota)
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
nmol/L
ng/ml
#
%
Deficient
< 50
< 20
192
37.5
Insufficient
50-72
20-29
197
38.5
> 72-374
30-150
123
24.0
> 374
>150
0
0
Sufficient
Toxic
Vitamin D Deficiency in Breast Cancer
Tumor and Treatment Related Factors Associated with Vitamin D
Factor
#
Vitamin D
(nmol/L)
p-value
Type of Surgery
Mastectomy
Lumpectomy
116
396
54.5
59.1
0.07
Tumor Stage
1
2
3
288
164
24
59.2
56.9
53.7
0.53
Nodal Involvement
None
≥1
342
98
58.7
56.7
0.41
Tumor Grade
1
2
3
77
212
180
63.4
58.8
55.0
0.03
Estrogen Receptor
Positive
Negative
342
98
57.9
58.3
0.90
Adjuvant CXT
No
Yes
313
199
60.1
54.9
0.02
Adjuvant Hormone
No
Yes
312
200
57.2
59.5
0.25
Vitamin D Deficiency in Breast Cancer
1.0
Distant Disease-Free Survival
Proportion distant disease free
0.2
0.4
0.6
0.8
Sufficient
Insufficient
Deficient
0.0
p=0.02
0
2
4
6
8
Years since diagnosis
10
12
Deficient
< 50 nmol/L
Insufficient
≥ 50-72 nmol/L
Sufficient
> 72 nmol/L
1.94
(1.16-3.25)
1.37
(0.80-2.33)
1.0
5 year
82%
85%
88%
10 Year
69%
79%
83%
HR
(95% CI)
Vitamin D Deficiency in Breast Cancer
1.0
Overall Survival
Sufficient
Proportion survived
0.4
0.6
0.8
Insufficient
0.2
Deficient
0.0
p=0.02
0
2
4
6
8
Years since diagnosis
10
12
Deficient
< 50 nmol/L
Insufficient
≥ 50-72 nmol/L
Sufficient
> 72 nmol/L
1.73
(1.05-2.86)
1.01
(0.59-1.73)
1.0
5 year
87%
93%
92%
10 Year
74%
85%
85%
HR
(95% CI)
Vitamin D Deficiency in Breast Cancer
1
0
-1
Log hazard of death
2
Overall Survival
Smoothed Log Hazard
50
100
150
25-Hydroxyvitamin D (nmol/L)
Vitamin D Deficiency in Breast Cancer
Conclusions
1.
Vitamin D deficiency/insufficiency was common at breast cancer
diagnosis. Only 24% had levels considered sufficient.
2.
Vitamin D deficiency was associated with higher grade tumors.
3.
Vitamin D deficiency was associated with an increased risk of distant
recurrence and death.
4.
Replication is recommended; an RCT of vitamin D supplementation
may be indicated if results are replicated.
5.
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.
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