Folic acid supplement use and breast cancer risk in BRCA1 and BRCA2 mutation carriers: a case-control study

Breast Cancer Res Treat. 2019 Apr;174(3):741-748. doi: 10.1007/s10549-018-05118-3. Epub 2019 Jan 2.


Purpose: Supplemental folic acid (the more bioavailable and synthetic form of folate) and breast cancer risk in BRCA mutation carriers have not been studied. We evaluated folic acid, vitamin B6 and vitamin B12 supplement use, and breast cancer risk among BRCA mutation carriers.

Methods: In this case-control study, dietary supplement use was collected from BRCA mutation carriers living in Canada. Supplement use was categorized as never or ever use. Total average daily supplement use was categorized as never, moderate, and high use based on tertiles. Unconditional logistic regression was used to estimate the odds ratio (OR) and 95% confidence intervals (CI) for supplement use and breast cancer risk.

Results: We included 129 breast cancer cases and 271 controls. Women who used any folic acid-containing supplement had a significantly decreased risk of breast cancer compared to women who never used a folic acid-containing supplement (OR 0.45; 95%CI 0.25, 0.79; P = 0.006). This was significant for BRCA1 mutation carriers only. The OR for moderate folic acid supplement intake was 0.39; P = 0.01, and high intake was 0.54; P = 0.09, compared to never users. Moderate vitamin B12 supplement intake was associated with decreased risk of breast cancer compared to never use (OR 0.48; 95%CI 0.24, 0.96; P = 0.04).

Conclusions: In this first investigation of folic acid supplement use and breast cancer risk in BRCA mutation carriers, these findings suggest that moderate folic acid- and vitamin B12-containing supplement use may be protective for BRCA-associated breast cancer, particularly among BRCA1 mutation carriers. Future studies with larger samples and prospective follow-up are needed.

Keywords: BRCA; Breast cancer; Folic acid; Multivitamin; Supplements.

MeSH terms

  • Adult
  • Aged
  • BRCA1 Protein / genetics*
  • BRCA2 Protein / genetics*
  • Breast Neoplasms / epidemiology*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / prevention & control
  • Canada
  • Case-Control Studies
  • Dietary Supplements
  • Female
  • Folic Acid / administration & dosage*
  • Humans
  • Logistic Models
  • Middle Aged
  • Mutation*
  • Odds Ratio
  • Prospective Studies
  • Vitamin B 12 / administration & dosage*
  • Vitamin B 6 / administration & dosage
  • Young Adult


  • BRCA1 Protein
  • BRCA1 protein, human
  • BRCA2 Protein
  • BRCA2 protein, human
  • Vitamin B 6
  • Folic Acid
  • Vitamin B 12