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


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High risk women with a BRCA1 mutation

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Checked People with a genetic mutation linked to cancer risk

Checked Previvors

Checked Women under 45

Checked Women over 45

Checked Special populations: Women with BRCA1 mutations


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Vitamins are an essential part of our diet. Vitamin supplements are often used to improve general health. This study explores how vitamin B supplements may affect breast cancer risk in women with BRCA mutations. (5/17/19)

Contents

At a glance In-depth
Findings     limitations            
Guidelines Resources and references
Questions for your doctor  


STUDY AT A GLANCE

This study is about:

whether B vitamins lower or raise breast cancer risk in women with BRCA mutations.

Why is this study important?

Vitamin supplement use is a common. Women with a BRCA mutation can adjust use of vitamins, which may have an impact on breast cancer risk.

Study findings: 

This is a small study that looked at vitamin B supplement use among 400 women in Canada who had a mutation in BRCA1 or BRCA2.

  • Women who took supplements that included folic acid (synthetic Vitatmin B9), Vitamin B complex, multivitamins, folic-acid specific, or prenatal vitamins - had decreased breast cancer risk compared to women who had never used these supplements if prior child birth history was considered Women who took these supplements had a 55% decrease in risk.
     
  • The decreased risk of breast cancer was observed in women who took moderate levels of folic acid (Vitamin B9) at 8-80 mcg/day or moderate levels of Vitamin B12 (.02-.34 mcg/day).
     
  • Vitamin B6 supplements did not significantly affect breast cancer risk.
     
  • Vitamin B significantly impacted women with BRCA1 mutations, but not women with BRCA2 mutations.

What does this mean for me?

If you are a woman with a BRCA1 mutation, use of Vitamin B9 (folic acid) and/or Vitamin B12 supplements may lower your breast cancer risk. This study suggest that folic acid taken at a level available in over-the-counter supplements may have an impact on breast risk in women with a BRCA mutation. 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.

It is also important to know that the United States Food and Drug Administration (FDA) regulates vitamins and other supplements as foods and not as drugs. This means that companies that make and sell vitamins do not have the same strict oversight. Speak with your health care provider before beginning any supplements. If you do decide to take supplements, look for reputable companies.  

What do the guidelines say?

Experts have created national guidelines that outline the medical options for women at high risk for breast cancer. These guidelines include:

  • Increased screening for breast cancer
  • Medications to reduce breast cancer risk
  • Risk-reducing mastectomy

You can read more about the guidelines here.

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Expert Guidelines

Guidelines for breast cancer risk management

The National Comprehensive Cancer Network (NCCN) is a panel of top cancer experts who create national guidelines detection, prevention and treatment of cancer. NCCN publishes guidelines for people at high risk for breast cancer due to an inherited mutation. The guidelines for women with a BRCA1 or BRCA2 mutation include:

Breast cancer screening

  • Learning to be aware of changes in breasts beginning at age 18
  • Clinical breast exam every 6-12 months beginning at age 25
  • Annual breast MRI with contrast (or mammogram if MRI is unavailable) beginning at age 25 
  • Annual breast MRI with contrast and mammogram at ages 30-75
  • Consider 3D mammography if available
  • Screening after age 75 should be considered on an individual basis
  • Consider participation in an imaging or screening clinical trial

Breast cancer risk reduction

  • Discussion of risk-reducing mastectomy
  • Consider medication to reduce breast cancer risk

You can read more about the guidelines here.

Dietary supplements

The National Comprehensive Cancer Network (NCCN) has guidelines on survivorship that include the following recommendations on supplement use:

  • Supplement use is not recommended for most survivors, except in instances of documented nutritional deficiencies, inadequate diet, or other indications (eg., osteoporosis).
  • Little data exist to support the use of vitamins or other dietary supplements for the purposes of cancer control, recurrence, or prevention. 
  • Taking vitamin supplements does not replace the need for a healthy diet. All efforts should be made to obtain nutrients from food and beverages.
  • Providers should assess supplement use at regular intervals. Ask about reasons for supplement use and supplement ingredients. 
  • Survivors of certain cancers (eg., gastrointestinal cancers) may be at risk for vitamin deficiencies based on their cancer treatment. Deficiencies should be asessed and addressed as needed. 

The American Institute for Cancer Research (AICR) is an organization that translates research on diet and cancer risk into practical information for the public. AICR recommends that people try to meet their nutritional needs through a healthy diet. They do not discourage people from taking a multivitamin supplement, but they warn people not to rely on supplements alone to protect from cancer. 

The American Cancer Society recommends speaking with your oncologist before taking any supplements. 

Questions To Ask Your Health Care Provider

  • Is it appropriate for me to use Vitamin B supplements?
  • How much Vitamin B should I take?
  • What impact will vitamin use have on my health? on my breast cancer risk?
  • Will increasing the Vitamin B in my diet make a difference?
  • Can you refer me to a nutritionist?

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 .4ยท      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.

Share your thoughts on this XRAYS article by taking our brief survey.

Posted 5/17/19

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