Study: Do Vitamin B supplements alter breast cancer risk for women with BRCA mutations?

IN-DEPTH REVIEW OF RESEARCH

Study background:

The B vitamins are a group of essential molecules that are commonly found in the same foods and contribute to key metabolic processes in cells. This study by Shana Kim and colleagues published in Breast Cancer Treatment and Research focuses on 3: Vitamins B6, B9 and B12. Vitamin B6 is involved in amino acid metabolism, the building blocks of proteins and in forming signaling molecules in the brain. Vitamin B9 (folate) and is involved in DNA metabolism and DNA repair and is essential for cell division. Folic acid, the synthetic version of folate found in supplements is slowly converted to folate in the body. Vitamin B12 is involved in metabolism of carbohydrates, lipids and proteins.

A lack of various B vitamins is associated with several diseases. Low Vitamin B6 levels are associated with skin and neurological problems. Low Vitamin B9 or folate levels can cause anemia and in pregnant women can lead to birth defects. Low Vitamin B12 levels can lead to anemia and cognitive problems.

The role of B vitamins in cancer is been controversial and complex. Some studies have observed that high folate levels and other B vitamins may be associated with cell growth in cultured cancer cells. A previous small prospective trial by the authors of this study suggested that women with BRCA mutations who had high levels of folate also had increased breast cancer risk compared to women with lower folate levels. Meta-studies of women in the general population suggested that there may be decreased breast cancer risk with moderate levels of Vitamin B and increased breast cancer risk with high levels of Vitamin B. Other studies suggest that folate may offset the increased risk of breast cancer associated with some alcohol intake.

Researchers of this study wanted to know:

whether Vitamin B supplements alter the breast cancer risk of women with BRCA mutations.

Populations looked at in this study:

This is a follow-up study of participants who had completed a standardized questionnaire between 1994 and 2016. Breast cancer was self-reported and pathology was confirmed in 50% of cases.  A second questionnaire was sent between September 2014 and September 2016 to women in this group who had BRCA mutations (with and without breast cancer) asking about their vitamin B supplement use. Among the 910 original participants, 512 (56%)  returned the second questionnaire. Based on their responses, potential participants of this study were eliminated from eligibility if they had a cancer prior to breast cancer, had a prior bilateral mastectomy, or if they did not provide information about their BRCA mutation status or supplement use. The final group of participants for this study were 400 women age 18-70 with a BRCA mutation living in Canada; 129 had breast cancer and 271 did not.

Study design:

This is a small case-control study. Researchers asked women with BRCA mutations (with and without breast cancer)  if they had ever used Vitamin B6, Vitamin B9 (folate or folic acid) or Vitamin B12 in any supplement and to describe their daily use was (never, moderate, or high use). Vitamin B doses were self-reported or inferred by researchers from reported use. Researchers evaluated women based on multiple factors including parity (whether they had given birth), alcohol consumption, mutation status and other health factors.

Study findings:  

• No association was made between breast cancer risk and multivitamin use or folic-acid specific supplements alone if childbirth was not considered.
• However, when adjusted for age and BRCA status, women who took prenatal vitamins during pregnancy had a significant 43% decrease in breast cancer risk compared to women who did not take prenatal vitamins. For this reason, researchers looked more carefully at how childbirth impacted data on breast cancer risk. They evaluated the overall data on supplement use for women with different child birth histories.
• Women who took any supplement that contained folic-acid (vitamin B complex, multivitamins, folic-acid specific, prenatal vitamins) had a significantly decreased breast cancer risk compared to women who never used these supplements if prior child birth history was considered (55% decrease, OR .4·      5, p value = .006).

Vitamin B9 (folate)

Women who took moderate levels of folic acid supplements (8-80 mcg/day) had significantly decreased risked compared to women who had never used supplements. This suggests that moderate folic acid supplements may be protective.

However, no significant difference was found between women who took high levels of folic acid supplements and those who did not take any. This suggests that too much folic acid is not protective.

Vitamin B12

Women with BRCA mutations who had taken moderate levels of Vitamin B12 supplements had a decreased risk of breast cancer (52% less) compared to women with BRCA mutations who never used Vitamin B12 supplements.

Vitamin B6

No significant differences in breast cancer risk were associated with different levels of Vitamin B6 intake.

Supplements may decrease risk for women with BRCA1 mutations but not those with BRCA2 mutations.

• Women with BRCA1 mutations who took folic-acid supplements had a 70% decreased risk of breast cancer compared to women with BRCA1 mutations who never took folic acid-supplements.
• Women with BRCA2 mutations who took folic-acid supplements had no significant difference in breast cancer risk compared to women with BRCA2 mutations who did not take folic-acid supplements.

Limitations:

This study is based on a small group of participants. Ideally, it should be repeated to see if these results are confirmed. Because only women with BRCA1 and BRCA2 were evaluated, tt is unclear if these results extend to women who do not have a BRCA1 or BRCA2 mutations and specifically what impact Vitamin B would have for women with mutation in other breast cancer predisposing genes.

This is a retrospective study that depends on participants' self-reporting of supplement use and any reporting inaccuracies may impact results. A prospective trial with larger numbers of participants would help to clarify the reliability of these findings. Ideally vitamin supplement use would be tracked prospectively tracked in detail, along with dietary consumption, to best assess their impact.

Response rate to the second questionnaire on supplement use was low (56%) -  which could introduce some bias if those responding differed from the larger group of participants. A difference may also have existed among those participants who were still living at the time of questionnaire (2014-2016) and the participants who were initially enrolled (1994 to 2016).

Dietary intake of Vitamin B was not assessed. Adequate dietary intake may substitute for vitamin B supplements for some women and remains to be tested for BRCA carriers.

This study suggests that high levels of vitamin B supplements may not beneficial; no significant change in breast cancer risk was found with high levels of Vitamin B9 or 12 use. These researchers previous prospective study showed that high circulating levels of folate (Vitamin B9) in the blood was associated with increased breast cancer risk. The data in this study suggests that while moderate levels of Vitamin B may be protective, high levels of Vitamin B may be harmful; a larger study is needed to clarify this issue. Meta-analyses of folate use in the general population suggest that very low or very high levels of folate are associated with increased breast cancer risk and moderate levels are associated with decreased breast cancer risk.

Conclusions:

Moderate levels of Vitamin B supplements may decrease risk of breast cancer for women with BRCA1 mutations.

It is important to note that current breast cancer risk-reducing guidelines for BRCA mutations carriers do not address the use of vitamin supplements. Experts do not recommend that women at high risk for breast cancer rely only on diet, exercise or nutritional supplements to lower their risk for cancer.

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Posted 5/17/19
 

References

Kim SJ, Zhang CXW, Demsky R, Armei S, Kim Y-I, Narod SA, Kotsopoulos J., "Folic acid supplement use and breast cancer risk in BRCA1 and BRCA2 mutation carriers: a case-control study". Breast Cancer Research and Treatment. January 2, 2019.
 

Disclosure

FORCE receives funding from industry sponsors, including companies that manufacture cancer drugs, tests and devices. All XRAYS articles are written independently of any sponsor and are reviewed by members of our Scientific Advisory Board prior to publication to assure scientific integrity.