There have been several prospective case-control and cohort studies that looked at breast cancer incidence as a function of prediagnostic serum 25(OH)D123456. In the case of breast cancer, only case-control studies, in which serum 25(OH)D level is determined at the time of diagnosis, and nested case-control studies with follow-up times less than five years have found statistically significant inverse correlations between serum 25(OH)D level and incidence7 8.
The data in these studies can be used to estimate the relationship between prediagnostic serum 25(OH)D and breast cancer incidence by combining the values for the mean serum 25(OH)D level in a preliminary meta-analysis, then trying various mathematical functions to see which has the best fit to the data.
A case-control study suggests that vitamin D is associated with a reduced risk of breast cancer regardless of estrogen receptor/progesterone receptor status of the tumor12.
In one NCCS of breast cancer incidence, the relative risk of cancer decreased with increasing follow-up time: 0.66 (95% CI, 0.46–0.94) for follow-up periods of 0–5 years, 0.73 (95% CI, 0.53–1.01) for 5–10 years, 0.99 (95% CI, 0.74–1.32) for 10–15 years, and 1.23 (95% CI, 0.86–1.75) for more than 15 years7.
There have also been a number of studies that investigated incidence of breast cancer with respect to oral vitamin D intake from diet and supplements. A case-control study from Italy found an odds ratio of 0.79 (95% CI, 0.70-0.90) for subjects in the highest three deciles of consumption compared to those in the lowest ones combined13.
A nested case-control study with a 10-year follow-up period found significant inverse correlations with estrogen receptor positive (ER+) or progesterone receptor positive breast cancer for >548 IU/d vitamin D vs. <162 IU/d, but not for either receptor negative breasat cancer14. This study also found a statistically significant inverse correlation with oral vitamin D intake for tumors >2 mm but not for <2 mm.
Another nested case-control study with an 8.5-year follow-up period found similar results for ER+ and ER-, although the risk ratio was not statistically significant15.
A study in France found a statistically significant inverse correlation for breast cancer incidence for >113 IU/d vitamin D vs. <80 IU/d16.
A study in New York State reported:
“We found that breast cancer cases had significantly lower 25OHD concentrations than controls (adjusted mean, 22.8 versus 26.2 ng/mL, p<0.001). Among premenopausal women, 25OHD concentrations were lower in those with high- versus low-grade tumors, and ER negative versus ER positive tumors (p≤0.03). Levels were lowest among women with triple-negative cancer (17.5 ng/mL), significantly different from those with luminal A cancer (24.5 ng/mL, p = 0.002). In case-control analyses, premenopausal women with 25OHD concentrations above the median had significantly lower odds of having triple-negative cancer (OR = 0.21, 95% CI = 0.08-0.53) than those with levels below the median; and every 10 ng/mL increase in serum 25OHD concentrations was associated with a 64% lower odds of having triple-negative cancer (OR = 0.36, 95% CI = 0.22-0.56). The differential associations by tumor subtypes among premenopausal women were confirmed in case-series analyses”17.
Thus, the evidence that vitamin D reduces the risk of breast cancer is strong.
Page last edited: 22 August 2011
- Abbas, S. Linseisen, J. Slanger, T. Kropp, S. Mutschelknauss, E. J. Flesch-Janys, D. Chang-Claude, J. Serum 25-hydroxyvitamin D and risk of post-menopausal breast cancer–results of a large case-control study. Carcinogenesis. 2008 Jan; 29 (1): 93-9.
- Abbas, S. Chang-Claude, J. Linseisen, J. Plasma 25-hydroxyvitamin D and premenopausal breast cancer risk in a German case-control study. Int J Cancer. 2009 Jan 1; 124 (1): 250-5.
- Bertone-Johnson, E. R. Vitamin D and breast cancer. Ann Epidemiol. 2009 Jul; 19 (7): 462-7.
- Crew, K. D. Gammon, M. D. Steck, S. E. Hershman, D. L. Cremers, S. Dworakowski, E. Shane, E. Terry, M. B. Desai, M. Teitelbaum, S. L. Neugut, A. I. Santella, R. M. Association between plasma 25-hydroxyvitamin D and breast cancer risk. Cancer Prev Res (Phila Pa). 2009 Jun; 2 (6): 598-604.
- Freedman, D. M. Chang, S. C. Falk, R. T. Purdue, M. P. Huang, W. Y. McCarty, C. A. Hollis, B. W. Graubard, B. I. Berg, C. D. Ziegler, R. G. Serum levels of vitamin D metabolites and breast cancer risk in the prostate, lung, colorectal, and ovarian cancer screening trial. Cancer Epidemiol Biomarkers Prev. 2008 Apr; 17 (4): 889-94.
- Lowe, L. C. Guy, M. Mansi, J. L. Peckitt, C. Bliss, J. Wilson, R. G. Colston, K. W. Plasma 25-hydroxy vitamin D concentrations, vitamin D receptor genotype and breast cancer risk in a UK Caucasian population. Eur J Cancer. 2005 May; 41 (8): 1164-9.
- Robien, K. Cutler, G. J. Lazovich, D. Vitamin D intake and breast cancer risk in postmenopausal women: the Iowa Women’s Health Study. Cancer Causes Control. 2007 Sep; 18 (7): 775-82.
- Grant, W. B. Effect of interval between serum draw and follow-up period on relative risk of cancer incidence with respect to 25-hydroxyvitamin D level; implications for meta-analyses and setting vitamin D guidelines. Dermato-endocrinology. 2011; 3 (3):
- Gandini, S. Boniol, M. Haukka, J. Byrnes, G. Cox, B. Sneyd, M. J. Mullie, P. Autier, P. Meta-analysis of observational studies of serum 25-hydroxyvitamin D levels and colorectal, breast and prostate cancer and colorectal adenoma. Int J Cancer. 2010 May 6;
- Grant, W. B. Relation between prediagnostic serum 25-hydroxyvitamin D level and incidence of breast, colorectal, and other cancers. J Photochem Photobiol B. 2010 May 12;
- Yin, L. Grandi, N. Raum, E. Haug, U. Arndt, V. Brenner, H. Meta-analysis: serum vitamin D and breast cancer risk. Eur J Cancer. 2010 Aug; 46 (12): 2196-205.
- Blackmore, K. M. Lesosky, M. Barnett, H. Raboud, J. M. Vieth, R. Knight, J. A. Vitamin D From Dietary Intake and Sunlight Exposure and the Risk of Hormone-Receptor-Defined Breast Cancer. Am J Epidemiol. 2010;
- Rossi, M. McLaughlin, J. K. Lagiou, P. Bosetti, C. Talamini, R. Lipworth, L. Giacosa, A. Montella, M. Franceschi, S. Negri, E. La Vecchia, C. Vitamin D intake and breast cancer risk: a case-control study in Italy. Ann Oncol. 2009 Feb; 20 (2): 374-8.
- Lin, J. Manson, J. E. Lee, I. M. Cook, N. R. Buring, J. E. Zhang, S. M. Intakes of calcium and vitamin D and breast cancer risk in women. Arch Intern Med. 2007 May 28; 167 (10): 1050-9.
- McCullough, M. L. Rodriguez, C. Diver, W. R. Feigelson, H. S. Stevens, V. L. Thun, M. J. Calle, E. E. Dairy, calcium, and vitamin D intake and postmenopausal breast cancer risk in the Cancer Prevention Study II Nutrition Cohort. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2005 Dec; 14 (12): 2898-904.
- Engel, P. Fagherazzi, G. Mesrine, S. Boutron-Ruault, M. C. Clavel-Chapelon, F. Joint Effects of Dietary Vitamin D and Sun Exposure on Breast Cancer Risk: Results from the French E3N Cohort. Cancer Epidemiol Biomarkers Prev. 2011 Jan; 20 (1): 187-98.
- Yao, S. Sucheston, L. E. Millen, A. E. Johnson, C. S. Trump, D. L. Nesline, M. K. Davis, W. Hong, C. C. McCann, S. E. Hwang, H. Kulkarni, S. Edge, S. B. O’Connor, T. L. Ambrosone, C. B. Pretreatment serum concentrations of 25-hydroxyvitamin D and breast cancer prognostic characteristics: a case-control and a case-series study. PLoS One. 2011; 6 (2): e17251.