Breast Cancer Research and Treatment

, Volume 141, Issue 3, pp 331–339 | Cite as

Blood levels of vitamin D and early stage breast cancer prognosis: a systematic review and meta-analysis

  • April A. N. Rose
  • Christine Elser
  • Marguerite Ennis
  • Pamela J. GoodwinEmail author


Vitamin D regulates expression of genes important in development and progression of breast cancer. The association of vitamin D with breast cancer outcomes among breast cancer patients is controversial. We conducted a systematic review and meta-analysis of this association in early stage breast cancer outcome. We searched MEDLINE (1982–May 1, 2013), the American Society of Clinical Oncology (2009–2012), and the San Antonio Breast Cancer Symposium (2010–2012) for abstracts, using the following keywords: “breast cancer” and “prognosis” or “survival”, and “vitamin D” or” calcitriol” to identify studies reporting the associations of blood vitamin D levels (drawn close to diagnosis) with breast cancer outcomes. Meta-analyses were performed using an inverse-variance weighted fixed-effects model with Stata Version 12. Eight studies including 5,691 patients were identified. Vitamin D deficiency was variably categorized across studies; a median of 36.8 % of patients were classified as deficient. Low vitamin D levels were associated with a pooled hazard ratio of 2.13 (95 % CI 1.64–2.78) and 1.76 (95 % CIs 1.35–2.30) for recurrence (six studies) and death (four studies), respectively, with no evidence of significant heterogeneity across studies. There was potential evidence of a publication bias in studies examining associations with death (but not in those examining associations with recurrence). These findings support an association of low levels of vitamin D with increased risk of recurrence and death in early stage breast cancer patients. Given the observational nature of the included studies, it cannot be concluded that this association is causal. Further research is warranted to investigate the potential beneficial effects of vitamin D in breast cancer.


Breast cancer Vitamin D Prognosis Meta-analysis 


Conflict of interest

The authors declare that there are no conflicts of interest.


  1. 1.
    Bauer SR, Hankinson SE, Bertone-Johnson ER, Ding EL (2012) Plasma vitamin D levels, menopause, and risk of breast cancer: dose-response meta-analysis of prospective studies. Medicine (Baltimore) 92(3):123–131. doi: 10.1097/MD.0b013e3182943bc2 Google Scholar
  2. 2.
    Holick MF (2007) Vitamin D deficiency. N Engl J Med 357(3):266–281. doi: 10.1056/NEJMra070553 PubMedCrossRefGoogle Scholar
  3. 3.
    Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK, Durazo-Arvizu RA, Gallagher JC, Gallo RL, Jones G, Kovacs CS, Mayne ST, Rosen CJ, Shapses SA (2010) The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab 96(1):53–58. doi: 10.1210/jc.2010-2704 PubMedCrossRefGoogle Scholar
  4. 4.
    Cescon DW, Ganz PA, Beddows S, Ennis M, Mills BK, Goodwin PJ (2012) Feasibility of a randomized controlled trial of vitamin D vs. placebo in women with recently diagnosed breast cancer. Breast Cancer Res Treat 134(2):759–767. doi: 10.1007/s10549-012-2120-7 PubMedCrossRefGoogle Scholar
  5. 5.
    Goodwin PJ, Ennis M, Pritchard KI, Koo J, Hood N (2009) Prognostic effects of 25-hydroxyvitamin D levels in early breast cancer. J Clin Oncol 27(23):3757–3763. doi: 10.1200/JCO.2008.20.0725 PubMedCrossRefGoogle Scholar
  6. 6.
    Clark AS CJ, Kapoor S, Esserman LJ, DeMichele A, and I-SPY TRIAL-1 Investigators (2012) Pretreatment vitamin D levels and response to neoadjuvant chemotherapy in the I-SPY 1 TRIAL. Cancer Res 72(24 Suppl):Abstract nr P3-06-10Google Scholar
  7. 7.
    Coleman RE RE, Marshall HC, Wilson C, Brown JE, Gossiel J, Gregory WM, Cameron D, Bell R (2012) Vitamin D, but not bone turnover markers, predict relapse in women with early breast cancer: an AZURE translational study. Cancer Res 72(24 Suppl):Abstract nr S6-4Google Scholar
  8. 8.
    Hatse S, Lambrechts D, Verstuyf A, Smeets A, Brouwers B, Vandorpe T, Brouckaert O, Peuteman G, Laenen A, Verlinden L, Kriebitzsch C, Dieudonne AS, Paridaens R, Neven P, Christiaens MR, Bouillon R, Wildiers H (2012) Vitamin D status at breast cancer diagnosis: correlation with tumor characteristics, disease outcome, and genetic determinants of vitamin D insufficiency. Carcinogenesis 33(7):1319–1326. doi: 10.1093/carcin/bgs187 PubMedCrossRefGoogle Scholar
  9. 9.
    Kim HJ, Lee YM, Ko BS, Lee JW, Yu JH, Son BH, Gong GY, Kim SB, Ahn SH (2011) Vitamin D deficiency is correlated with poor outcomes in patients with luminal-type breast cancer. Ann Surg Oncol 18(7):1830–1836. doi: 10.1245/s10434-010-1465-6 PubMedCrossRefGoogle Scholar
  10. 10.
    Tretli S, Schwartz GG, Torjesen PA, Robsahm TE (2012) Serum levels of 25-hydroxyvitamin D and survival in Norwegian patients with cancer of breast, colon, lung, and lymphoma: a population-based study. Cancer Causes Control 23(2):363–370. doi: 10.1007/s10552-011-9885-6 PubMedCrossRefGoogle Scholar
  11. 11.
    Villasenor A, Ballard-Barbash R, Ambs A, Bernstein L, Baumgartner K, Baumgartner R, Ulrich CM, Hollis BW, McTiernan A, Neuhouser ML (2013) Associations of serum 25-hydroxyvitamin D with overall and breast cancer-specific mortality in a multiethnic cohort of breast cancer survivors. Cancer Causes Control 24(4):759–767. doi: 10.1007/s10552-013-0158-4 PubMedCrossRefGoogle Scholar
  12. 12.
    Vrieling A, Hein R, Abbas S, Schneeweiss A, Flesch-Janys D, Chang-Claude J (2011) Serum 25-hydroxyvitamin D and postmenopausal breast cancer survival: a prospective patient cohort study. Breast Cancer Res 13(4):R74. doi: 10.1186/bcr2920 PubMedCrossRefGoogle Scholar
  13. 13.
    Freedman DM, Looker AC, Abnet CC, Linet MS, Graubard BI (2010) Serum 25-hydroxyvitamin D and cancer mortality in the NHANES III study (1988-2006). Cancer Res 70(21):8587–8597. doi: 10.1158/0008-5472.CAN-10-1420 PubMedCrossRefGoogle Scholar
  14. 14.
    Rosen CJ, Adams JS, Bikle DD, Black DM, Demay MB, Manson JE, Murad MH, Kovacs CS (2012) The nonskeletal effects of vitamin D: an Endocrine Society scientific statement. Endocr Rev 33(3):456–492PubMedCrossRefGoogle Scholar
  15. 15.
    Protani M, Coory M, Martin JH (2010) Effect of obesity on survival of women with breast cancer: systematic review and meta-analysis. Breast Cancer Res Treat 123(3):627–635. doi: 10.1007/s10549-010-0990-0 PubMedCrossRefGoogle Scholar
  16. 16.
    Niraula S, Ocana A, Ennis M, Goodwin PJ (2012) Body size and breast cancer prognosis in relation to hormone receptor and menopausal status: a meta-analysis. Breast Cancer Res Treat 134(2):769–781. doi: 10.1007/s10549-012-2073-x PubMedCrossRefGoogle Scholar
  17. 17.
    Holmes MD, Chen WY, Feskanich D, Kroenke CH, Colditz GA (2005) Physical activity and survival after breast cancer diagnosis. JAMA 293(20):2479–2486PubMedCrossRefGoogle Scholar
  18. 18.
    Holick CN, Newcomb PA, Trentham-Dietz A, Titus-Ernstoff L, Bersch AJ, Stampfer MJ, Baron JA, Egan KM, Willett WC (2008) Physical activity and survival after diagnosis of invasive breast cancer. Cancer Epidemiol Biomarkers Prev 17(2):379–386PubMedCrossRefGoogle Scholar
  19. 19.
    Irwin ML, Smith AW, McTiernan A, Ballard-Barbash R, Cronin K, Gilliland FD, Baumgartner RN, Baumgartner KB, Bernstein L (2008) Influence of pre- and postdiagnosis physical activity on mortality in breast cancer survivors: the health, eating, activity, and lifestyle study. J Clin Oncol 26(24):3958–3964PubMedCrossRefGoogle Scholar
  20. 20.
    Pino AM, Rodriguez JM, Rios S, Astudillo P, Leiva L, Seitz G, Fernandez M, Rodriguez JP (2006) Aromatase activity of human mesenchymal stem cells is stimulated by early differentiation, vitamin D and leptin. J Endocrinol 191(3):715–725PubMedCrossRefGoogle Scholar
  21. 21.
    Dizdar O, Bulut N, Altundag K (2008) Vitamin D supplementation and response to aromatase inhibitors in postmenopausal women with hormone-receptor positive breast cancer. Breast 17(2):120PubMedCrossRefGoogle Scholar
  22. 22.
    Picotto G, Liaudat AC, Bohl L, Tolosa de Talamoni N (2012) Molecular aspects of vitamin D anticancer activity. Cancer Invest 30(8):604–614. doi: 10.3109/07357907.2012.721039 PubMedCrossRefGoogle Scholar
  23. 23.
    Shao T, Klein P, Grossbard ML (2012) Vitamin D and breast cancer. Oncologist 17(1):36–45. doi: 10.1634/theoncologist.2011-0278 PubMedCrossRefGoogle Scholar
  24. 24.
    Stambolsky P, Tabach Y, Fontemaggi G, Weisz L, Maor-Aloni R, Siegfried Z, Shiff I, Kogan I, Shay M, Kalo E, Blandino G, Simon I, Oren M, Rotter V (2010) Modulation of the vitamin D3 response by cancer-associated mutant p53. Cancer Cell 17(3):273–285PubMedCrossRefGoogle Scholar
  25. 25.
    Ahn J, Peters U, Albanes D, Purdue MP, Abnet CC, Chatterjee N, Horst RL, Hollis BW, Huang WY, Shikany JM, Hayes RB (2008) Serum vitamin D concentration and prostate cancer risk: a nested case-control study. J Natl Cancer Inst 100(11):796–804. doi: 10.1093/jnci/djn152 PubMedCrossRefGoogle Scholar
  26. 26.
    Ahn J, Yu K, Stolzenberg-Solomon R, Simon KC, McCullough ML, Gallicchio L, Jacobs EJ, Ascherio A, Helzlsouer K, Jacobs KB, Li Q, Weinstein SJ, Purdue M, Virtamo J, Horst R, Wheeler W, Chanock S, Hunter DJ, Hayes RB, Kraft P, Albanes D (2010) Genome-wide association study of circulating vitamin D levels. Hum Mol Genet 19(13):2739–2745PubMedCrossRefGoogle Scholar
  27. 27.
    Brock KE, Graubard BI, Fraser DR, Weinstein SJ, Stolzenberg-Solomon RZ, Lim U, Tangrea JA, Virtamo J, Ke L, Snyder K, Albanes D (2010) Predictors of vitamin D biochemical status in a large sample of middle-aged male smokers in Finland. Eur J Clin Nutr 64(3):280–288PubMedCrossRefGoogle Scholar
  28. 28.
    Peppone LJ, Rickles AS, Janelsins MC, Insalaco MR, Skinner KA (2012) The association between breast cancer prognostic indicators and serum 25-OH vitamin D levels. Ann Surg Oncol 19(8):2590–2599. doi: 10.1245/s10434-012-2297-3 PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • April A. N. Rose
    • 1
    • 2
  • Christine Elser
    • 3
  • Marguerite Ennis
    • 4
  • Pamela J. Goodwin
    • 3
    • 5
    Email author
  1. 1.Faculty of MedicineMcGill UniversityMontrealCanada
  2. 2.Goodman Cancer Research CentreMcGill UniversityMontrealCanada
  3. 3.Division of Medical Oncology and Hematology, Department of Medicine, Mount Sinai Hospital and The Princess Margaret Cancer CenterUniversity of TorontoTorontoCanada
  4. 4.Applied StatisticianMarkhamCanada
  5. 5.Division of Clinical Epidemiology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai HospitalUniversity of TorontoTorontoCanada

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