Breast Cancer Research and Treatment

, Volume 132, Issue 1, pp 243–250 | Cite as

Folate intake and breast cancer mortality in a cohort of Swedish women

  • Holly R. HarrisEmail author
  • Leif Bergkvist
  • Alicja Wolk


Folate may influence breast cancer development and progression through its role in one-carbon metabolism. However, epidemiologic data on the relation between folate and breast cancer survival are limited. We investigated whether dietary folate intake was associated with survival in 3,116 women diagnosed with breast cancer in the population-based Swedish Mammography Cohort. Participants completed a 67-item food frequency questionnaire in 1987. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for death from breast cancer and death from any cause. During 25,716 person-years of follow-up from 1987 to 2008, there were 852 deaths with 381 breast cancer deaths. Dietary folate intake was inversely associated with breast cancer and overall mortality. Women in the highest quartile of folate intake had a multivariable HR (95% CI) of death from breast cancer of 0.78 (0.58–1.03) compared to those in the lowest quartile (P trend = 0.03). The corresponding HR (95% CI) for death from any cause was 0.79 (0.66–0.96; P trend = 0.004). The protective association between dietary folate intake and breast cancer death was strongest among those with ER-negative tumors (HR = 0.42; 95% = CI 0.22–0.79; P trend = 0.01) comparing the highest to lowest quartile. Our findings suggest that folate intake before breast cancer diagnosis may improve breast cancer and overall survival. While these findings need to be confirmed in future studies, they do offer assurance that dietary folate intake at the levels observed in our population does not unfavorably affect survival after breast cancer.


Breast cancer Survival Folate Diet 



Swedish mammography cohort


Body mass index


Standard deviation


Estrogen receptor


Progesterone receptor


Food frequency questionnaire


International classification of diseases


Hazard ratio


Confidence interval



This study was supported by the Swedish Cancer Foundation, the Swedish Research Council/Committee for Infrastructure, and the Swedish Foundation for International Cooperation in Research and Higher Education. H.R.H. was supported by NIH training grant T32 ES007069 and MCHB grant 5T76MC00001 (formerly MCJ201).

Conflicts of interest



  1. 1.
    Patterson RE, Cadmus LA, Emond JA, Pierce JP (2010) Physical activity, diet, adiposity and female breast cancer prognosis: a review of the epidemiologic literature. Maturitas 66(1):5–15PubMedCrossRefGoogle Scholar
  2. 2.
    Mason JB, Choi S-W (2000) Folate and carcinogenesis: developing a unifying hypothesis. Adv Enzyme Regul 40(1):127–141PubMedCrossRefGoogle Scholar
  3. 3.
    Holmes MD, Stampfer MJ, Colditz GA, Rosner B, Hunter DJ, Willett WC (1999) Dietary factors and the survival of women with breast carcinoma. Cancer 86(5):826–835PubMedCrossRefGoogle Scholar
  4. 4.
    McEligot A, Largent J, Ziogas A, Peel D, Anton-Culver H (2006) Dietary fat, fiber, vegetable, and micronutrients are associated with overall survival in postmenopausal women diagnosed with breast cancer. Nutr Cancer 55(2):132–140PubMedCrossRefGoogle Scholar
  5. 5.
    Xu X, Gammon MD, Wetmur JG, Bradshaw PT, Teitelbaum SL, Neugut AI, Santella RM, Chen J (2008) B-vitamin intake, one-carbon metabolism, and survival in a population-based study of women with breast cancer. Cancer Epidemiol Biomarkers Prev 17(8):2109–2116PubMedCrossRefGoogle Scholar
  6. 6.
    Saquib J, Rock CL, Natarajan L, Saquib N, Newman VA, Patterson RE, Thomson CA, Al-Delaimy WK, Pierce JP (2011) Dietary intake, supplement use, and survival among women diagnosed with early-stage breast cancer. Nutr Cancer 63(3):327–333PubMedCrossRefGoogle Scholar
  7. 7.
    Sellers TA, Alberts SR, Vierkant RA, Grabrick DM, Cerhan JR, Vachon CM, Olson JE, Kushi LH, Potter JD (2002) High-folate diets and breast cancer survival in a prospective cohort study. Nutr Cancer 44(2):139–144PubMedCrossRefGoogle Scholar
  8. 8.
    Wolk A, Larsson SC, Johansson J-E, Ekman P (2006) Long-term fatty fish consumption and renal cell carcinoma incidence in women. JAMA 296(11):1371–1376PubMedCrossRefGoogle Scholar
  9. 9.
    Mattsson B, Wallgren A (1984) Completeness of the Swedish Cancer Register. Non-notified cancer cases recorded on death certificates in 1978. Acta Radiol Oncol 23:305–313PubMedCrossRefGoogle Scholar
  10. 10.
    Larsson SC, Bergkvist L, Wolk A (2009) Long-term meat intake and risk of breast cancer by oestrogen and progesterone receptor status in a cohort of Swedish women. Eur J Cancer 45(17):3042–3046PubMedCrossRefGoogle Scholar
  11. 11.
    Bergström L, Kylberg E, Hagman U, Erikson H, Bruce Å (1991) The food composition database KOST: the National Food Administration’s Information System for nutritive values of food. Vår Fö da 43:439–447Google Scholar
  12. 12.
    Willett W, Stampfer MJ (1986) Total energy intake: implications for epidemiologic analyses. Am J Epidemiol 124(1):17–27PubMedGoogle Scholar
  13. 13.
    Ludvigsson J, Otterblad-Olausson P, Pettersson B, Ekbom A (2009) The Swedish personal identity number: possibilities and pitfalls in healthcare and medical research. Eur J Epidemiol 24(11):659–667PubMedCrossRefGoogle Scholar
  14. 14.
    Larsson SC, Bergkvist L, Wolk A (2008) Folate intake and risk of breast cancer by estrogen and progesterone receptor status in a Swedish cohort. Cancer Epidemiol Biomarkers Prev 17(12):3444–3449PubMedCrossRefGoogle Scholar
  15. 15.
    Larsson SC, Åkesson A, Bergkvist L, Wolk A (2010) Multivitamin use and breast cancer incidence in a prospective cohort of Swedish women. Am J Clin Nutr 91(5):1268–1272PubMedCrossRefGoogle Scholar
  16. 16.
    Lamprecht SA, Lipkin M (2003) Chemoprevention of colon cancer by calcium, vitamin D and folate: molecular mechanisms. Nat Rev Cancer 3(8):601–614PubMedCrossRefGoogle Scholar
  17. 17.
    Kim Y-I (2003) Role of folate in colon cancer development and progression. J Nutr 133(11):3731S–3739SPubMedGoogle Scholar
  18. 18.
    Kim Y-I (2006) Folate: a magic bullet or a double edged sword for colorectal cancer prevention? Gut 55(10):1387–1389PubMedCrossRefGoogle Scholar
  19. 19.
    Kotsopoulos J, Medline A, Renlund R, Sohn K-J, Martin R, Hwang SW, Lu S, Archer MC, Kim Y-I (2005) Effects of dietary folate on the development and progression of mammary tumors in rats. Carcinogenesis 26(9):1603–1612PubMedCrossRefGoogle Scholar
  20. 20.
    Cho E, Holmes M, Hankinson SE, Willett WC (2007) Nutrients involved in one-carbon metabolism and risk of breast cancer among premenopausal women. Cancer Epidemiol Biomarkers Prev 16(12):2787–2790PubMedCrossRefGoogle Scholar
  21. 21.
    Lin J, Lee I-M, Cook NR, Selhub J, Manson JE, Buring JE, Zhang SM (2008) Plasma folate, vitamin B-6, vitamin B-12, and risk of breast cancer in women. Am J Clin Nutr 87(3):734–743PubMedGoogle Scholar
  22. 22.
    Sellers TA, Vierkant RA, Cerhan JR, Gapstur SM, Vachon CM, Olson JE, Pankratz VS, Kushi LH, Folsom AR (2002) Interaction of dietary folate intake, alcohol, and risk of hormone receptor-defined breast cancer in a prospective study of postmenopausal women. Cancer Epidemiol Biomarkers Prev 11(10):1104–1107PubMedGoogle Scholar
  23. 23.
    Zhang SM, Hankinson SE, Hunter DJ, Giovannucci EL, Colditz GA, Willett WC (2005) Folate intake and risk of breast cancer characterized by hormone receptor status. Cancer Epidemiol Biomarkers Prev 14(8):2004–2008PubMedCrossRefGoogle Scholar
  24. 24.
    Ferguson AT, Lapidus RG, Baylin SB, Davidson NE (1995) Demethylation of the estrogen receptor gene in estrogen receptor-negative breast cancer cells can reactivate estrogen receptor gene expression. Cancer Res 55(11):2279–2283PubMedGoogle Scholar
  25. 25.
    Lapidus RG, Nass SJ, Butash KA, Parl FF, Weitzman SA, Graff JG, Herman JG, Davidson NE (1998) Mapping of ER gene CpG island methylation by methylation-specific polymerase chain reaction. Cancer Res 58(12):2515–2519PubMedGoogle Scholar
  26. 26.
    Maunsell E, Drolet M, Brisson J, Robert J, Deschênes L (2002) Dietary change after breast cancer: extent, predictors, and relation with psychological distress. J Clin Oncol 20(4):1017–1025PubMedCrossRefGoogle Scholar
  27. 27.
    Salminen EK, Lagstrom HK (2000) Does breast cancer change patients’ dietary habits? Eur J Clin Nutr 54(11):844PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • Holly R. Harris
    • 1
    • 2
    Email author
  • Leif Bergkvist
    • 3
  • Alicja Wolk
    • 1
  1. 1.Division of Nutritional EpidemiologyThe National Institute for Environmental Medicine, Karolinska InstitutetStockholmSweden
  2. 2.Obstetrics and Gynecology Epidemiology CenterBrigham and Women’s HospitalBostonUSA
  3. 3.Department of Surgery and Centre for Clinical ResearchCentral HospitalVästeråsSweden

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