ACS Research Highlights

21 Metabolites May Be Linked with Postmenopausal Breast Cancer

Using blood samples collected from CPS-II Nutrition substudy participants, researchers identified new metabolites that may affect the risk of breast cancer.

The Challenge

The development of breast cancer has historically been 2 to 3 times higher in developed nations, including the United States, Australia, and Japan, compared to developing ones, including Ethiopia, Afghanistan, and Haiti. By the early 2000s, epidemiologists had identified risk factors for breast cancer that explain up to half of the excess risk within developed nations. Explanations for the remaining half, however, are still unclear.

Some evidence indicates that a cell's metabolism—how it synthesizes and breaks down fatty acids, for instance—may be important to the development of breast cancer. More recently, researchers have found an association between breast cancer and many different metabolites, that are either synthesized by the human body, or derived, from diet.

The Research

American Cancer Society (ACS) researcher Ying Wang, PhD, recently collaborated with fellow researchers from the ACS, the National Cancer Institute (NCI), and two other institutions to use metabolomics to identify risk factors for breast cancer. Metabolomics is the study of small molecules, called metabolites, that result from a cell’s metabolism. The body makes and stores metabolites as it breaks down food, drugs, or its own tissue. Metabolites are affected by the environment and diseases like cancer.

Wang and her fellow researchers used survey data and blood samples from participants in the Cancer Prevention Study-II (CPS-II) Nutrition Cohort. One group included 782 postmenopausal women who had been diagnosed with breast cancer and the other included 782 women who did not have breast cancer. Their average age was 68 and 98% of them were White.

The researchers measured the levels of 1,275 metabolites in the women’s blood samples that were taken before any diagnosis of cancer.

We found 21 new metabolites associated with a higher or lower risk for developing breast cancer after menopause. One of those is a polyphenol metabolite linked with eating fruit and a decreased risk for developing breast cancer."

Ying Wang, PhD

Senior Principal Scientist, Epidemiology

Population Science, American Cancer Society

To gauge the women’s risks for breast cancer, they used these measurements along with answers to survey questions about known risks for breast cancer. Some of the data they received from the surveys included BMI, the age they started their periods, the number of children they gave birth to and the age they were when they delivered them, and the age they reached menopause.

Then they compared this blood and survey data between the women who did and didn’t develop breast cancer.

They published their findings in the journal Metabolites. 

"We studied 1,275 metabolites and found 24 associated with a higher or lower risk for developing breast cancer after menopause," Wang explains. "Our findings of an increased risk for 3 hormonal metabolites confirms findings from earlier studies." 

The other 21 were new, she says, including a polyphenol metabolite that’s linked with eating fruit and a decreased risk of developing breast cancer. "Now, these new metabolites need to be confirmed by other studies, and all need more analysis so we can better understand their role in the development of breast cancer," Wang says.

They found levels of 24 distinct metabolites were associated with the risk of postmenopausal breast cancer.

  • No carbohydrate, energy, or peptide (short chains of amino acids that organize into proteins) metabolites were significantly associated with breast cancer.
  • 9 metabolites were found to increase the risk of breast cancer. Of those, 3 were hormonal metabolites linked to an increased risk for breast cancer that confirmed findings from previous studies.
  • 15 metabolites were found to help protect against breast cancer. For one of these, 4-allyphenol sulfate (a nonspecific microbial metabolite of polyphenols, which are compounds found in certain plant-based foods), the researchers found a correlation between eating fruit, such as apples and blueberries, and a lower risk of breast cancer.

Why It Matters 

These findings contribute to growing data on a link between certain metabolites and breast cancer. The results point out metabolites that deserve future validation efforts.

The results of this study suggest the pathways of these metabolites might be new targets for prevention efforts, and knowing these metabolites could help improve breast cancer risk-prediction models.