Study: Is asparagus linked to breast cancer metastasis?


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A new study published in the journal Nature shows that asparagine, a protein building block that takes its name from asparagus, promotes the spread of breast cancer in mice. The study by cancer experts from Britain, Canada and the U.S. investigated whether limiting the levels of asparagine in mice could reduce tumor metastasis. (3/2/18)

Contents

At a glance                  Questions for your doctor
Findings               Limitations              
Guidelines Resources and reference


STUDY AT A GLANCE

This study is about: 

Identifying new targets that reduce the ability of breast cancer cells to spread and become metastatic.

Why is this study important?

Breast cancer becomes deadly when it metastasizes—cancer cells leave the breast, enter the blood stream and then invade a secondary site such the brain, lungs or other organs.  This study suggests that reducing the amount of the amino acid asparagine may be one way to decrease the likelihood of breast cancer becoming metastatic.

Study findings: 

In mice that were bred to develop breast cancer:

  • limiting asparagine by either experimental approaches or diet reduced breast cancer metastasis.
  • increasing asparagine by either experimental approaches or diet increased breast cancer metastasis

“When the availability of asparagine was reduced, we saw little impact on the primary tumor in the breast [in mice], but tumor cells had reduced capacity for metastases in other parts of the body," said Greg Hannon, lead study author and Cambridge University cancer researcher.

What does this mean for me?

Breast cancer that stays confined to the breast is not deadly. But it is more difficult to treat and can become fatal if it metastasizes—if cancer cells spread beyond the tumor and into other organs in the body. These preliminary study results imply that reducing bodily amounts of asparagine is one way to decrease the risk of breast cancer metastasis. This result, however, needs to be confirmed by other studies. In addition, it is important to remember that  animal models of breast cancer do not always mimic the disease in humans.

Even if future guidelines were to support a reduction of asparagine to decrease the risk of breast cancer metastasis, it is virtually impossible to eliminate the substance from your diet. Foods rich in asparagine include not only asparagus, but also dairy, beef, poultry, eggs, fish, seafood, potatoes, legumes, nuts, seeds, soy and whole grains.  Experts agree that you should not drastically change your diet in an attempt to reduce the amount of asparagine you consume. Asparagine is found in all protein rich foods-many of which are considered part of a healthy diet.  In addition, your body naturally makes asparagine.  If you are concerned about how your diet will affect your outcome consider discussing this with your doctor or a nutritionist.

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Expert Guidelines

The National Comprehensive Cancer Network (NCCN) creates guidelines for cancer survivorship. Their survivorship guidelines on nutriation and weight management recommend:

  • Assessing dietary intake of fruits, vegetables and unrefined grains, as well as red and processed meats, alcohol, and processed foods or beverages with added fats and/or sugars. 
  • Assess eating habits, including portion size, night grazing, snacking habits, frequency of eating out and use of added fats or sugars to foods or beverages
  • All survivors should be encouraged to:
    • Make informed choices about food to ensure variety and adequate nutrient intake
    • Limit refined sugars
    • Eat a diet that is at least 50% plant-based, with the majority of food being vegetables, fruit and whole grains
    • Track calorie intake
      • Self-monitoring of caloric intake is an effective strategy for weight management
    • Minimize alcohol intake
      • Limit intake to no more than one drink per day for a woman and two drinks per day for a man
  • For patients desiring further recommendations for dietary guidelines, the USDA approvimate food plate volumes are:
    • Vegetables and fruits should comprise half the volume of food on the plate
    • Vegetables: 30% of plate; Fruits 20% of plate
    • Whole grains: 30% of plate
    • Protein: 20% of plate
  • Recommended sources of dietary components:
    • Fat: plant sources such as olive or canola oil, avocados, seeds and nuts, and fatty fish
    • Carbohydrates: fruits, vegetables, whole grains and legumes
    • Protein: poultry, fish, legumes, low-fat dairy foods, and nuts

The American Cancer Society recommendations on nutrition and physical activity include:

  • Achieve and maintain a healthy weight throughout life.
  • Adopt a physically active lifestyle.
  • Consume a healthy diet with an emphasis on plant-based foods
  • Limit the amount of processed and red meats:
    • Eat at least 2.5 cups of vegetables and fruits a day.
    • Chose whole grains instead of refined grain products.
    • Drink no more than 1 alcoholic drink per day (women).

Other experts also provide guidelines for nutrition and health, including:

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Questions To Ask Your Health Care Provider

  • Can my diet affect my risk for breast cancer metastasis?
  • What should I be eating to maximize my health and ability to tolerate treatment?
  • Can you provide me with a referral to a nutritionist?

Open Clinical Trials

  • NCT02334085 The Health of Women Study (HOW). This study conducted by Dr. Susan Love is recruiting men and women 18 years and older with and without breast cancer to assess factors including diet that influence the risk of breast cancer. Participation is via online survey.

The following clinical trials on diet or nutrition are currently recruiting participants with breast cancer to look at impact on treatment and outcomes:

IN-DEPTH REVIEW OF RESEARCH

Study background:

Preventing or eliminating metastasis is an important goal of breast cancer treatment. Mouse models of breast cancer are often used to better understand how breast cancers metastasize and to identify potential targets for treatment that can reduce or eliminate the metastatic potential of breast cancer cells. 

Asparagine is an amino acid that is a building block for proteins. Found in many foods, it is also made in the body by a cellular enzyme called asparagine synthetase. This study evaluated the effect of asparagine, either in the diet or produced by the naturally occurring enzyme asparagine synthetase, on breast cancer metastasis.

Researchers of this study wanted to know:

Which molecules can cause breast cancer cells to metastasize?

Population(s) looked at in the study:

This study used mice models of metastatic breast cancer. In addition, researchers looked at levels of asparagine synthetase in breast cancer patients and in a small sample of matched breast tumor and lung metastasis samples.
 

Study findings: 

Initially the study authors used sophisticated in vitro (test tube) techniques to identify molecules that may cause metastasis. Among the top candidates, asparagine synthetase appeared to play a critical role. The researchers then conducted multiple areas of related mouse study:

  • Mice that were predisposed to breast cancer were intravenously injected with special breast cancer cells which had low levels of asparagine synthetase. These cells had reduced levels of asparagine).  Control mice were injected with breast tumor cells with normal amounts of asparagine synthetase and asparagine.
    • Mice with reduced asparagine synthetase had significantly fewer lung metastases than control mice.
  • Fat pads of mice that were predisposed to breast cancer were directly injected with breast cancer cells in which the function of asparagine synthetase was experimentally reduced (thereby reducing the level of asparagine).
    • No significant change in the development of primary breast tumors was observed; however, lung metastasis was significantly reduced compared to mice in the control group.
  • Mice predisposed to breast cancer once breast tumors appeared were treated 5 times per week for 19 days with L-asparaginase, a chemotherapy drug that blocks the production of asparagine and is currently used to treat acute lymphoblastic leukemia, which is known to thrive on asparagine.
    • Although no significant difference was detected in the primary tumor, metastasis was reduced in mice treated with L-asparaginase compared to controls.
  • Mice that were predisposed to develop breast cancer were fed a diet that was either low or high in asparagine.   
    • Dietary asparagine did not affect the primary tumors, however, mice with a low-asparagine diet had a lower metastatic burden than mice with a high-asparagine diet.

Interestingly, when the study authors reviewed records of breast cancer patients (gene expression data from 2 data sets as well as a small number of matched breast tumors and lung metastases), they found that breast tumors with the highest levels of asparagine synthetase were most likely to metastasize, especially to the lymph nodes, brain, liver, and lungs.

Limitations:

It is important to remember that cancer therapies that work well in rodents don’t always translate to humans. While it is possible that dietary intake of asparagine may influence metastatic potential of breast cancer in humans, this hypothesis needs to be validated in human studies. 

Conclusions:

Asparagine is a non-essential amino acid that our bodies naturally synthesize. This new study suggests that decreasing levels of asparagine in mice reduces metastasis. If after further study, reduction of asparagine levels proves to reduce the metastatic potential of human breast cancer, other methods to reduce cellular availability of asparagine may need to be developed, because regulating dietary levels of asparagine would be extremely difficult, if not impossible. 

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Posted 3/2/18

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