Researchers Find Evidence That Diet Can Alter the Microbiome to Affect Breast Cancer Risk

June 2, 2021

When people think of microbiome, they typically think about the gut, but there’s also a breast microbiome, and the role it plays in breast health and breast cancer isn’t thoroughly understood. A microbiome is the collection of microorganisms that live in a particular environment in the body.

In 2018, scientists at Wake Forest School of Medicine, part of Wake Forest Baptist Health, showed that diet can influence the breast microbiome, demonstrating that like the gut microbiome, the breast microbiota can respond to diet.

Now, new research shows that diet, including fish oil supplements, can alter not only the breast microbiome, but also breast cancer tumors. The study appears online in Cancer Research, a journal of the American Association for Cancer Research.

To gain a better understanding of the relationship between microbiome, diet and cancer risk, researchers undertook a multi-prong approach to study both animal models and breast cancer patients.

“Obesity, typically associated with a high-fat diet consumption, is a well-known risk factor in postmenopausal breast cancer,” said Katherine L. Cook, Ph.D., assistant professor in the surgery – hypertension and cancer biology departments at Wake Forest School of Medicine. “But there’s still a lot we don’t know about the obesity link to microbiomes and the impact on breast cancer and patient outcomes.”

In the first part of the study, mice susceptible to breast cancer were fed either a high-fat or a low-fat diet. Mice consuming the high-fat diet had more tumors, which also developed more quickly and were larger than the tumors in the group receiving the low-fat diet. 

Next, to study the microbiome, researchers performed fecal transplants. Mice consuming the low-fat diet received the high-fat diet microbiome transplant, and mice consuming the high-fat diet received the low-fat diet microbiome transplant. Surprisingly, mice that consumed the low-fat diet and received a high-fat diet microbiome had just as many breast tumors as mice that had consumed the high-fat diet.

“Simply replacing the low-fat diet gut microbiome to the microbiome of high-fat diet consuming animals was enough to increase breast cancer risk in our models,” Cook said. “These results highlight the link between the microbiome and breast health.”

What’s the significance for breast cancer patients? Researchers also conducted a double-blind placebo-controlled clinical trial with breast cancer patients. Patients either received placebo or fish oil supplements for approximately two to four weeks before lumpectomy or mastectomy. 

Results showed that fish oil supplementation significantly modified the breast microbiome in both non-cancerous and malignant breast tissue. For example, scientists found longer-term administration of fish oil supplements (four weeks) increased the proportional abundance of Lactobacillus in the normal tumor-adjacent breast tissue. Lactobacillus is a genus of bacteria shown to decrease breast cancer tumor growth in preclinical models, suggesting potential anti-cancer properties of this intervention. Researchers also found decreased proportional abundance of Bacteroidales and Ruminococcus microbes in the breast tumors of patients taking the supplements, but the significance is unknown.

“This study provides additional evidence that diet plays a critical role in shaping the gut and breast microbiomes,” Cook said. “Ultimately, our study highlights that potential dietary interventions might reduce breast cancer risk.”

Cook’s team is also conducting additional studies on whether probiotic supplements can affect microbiome populations in mammary glands and in breast tumors.

This research is supported by the Chronic Disease Research Fund; American Cancer Society Research Scholar grants RSG-16-204-01-NEC and 133727-RSG-19-150-01-LIB; Susan G. Komen Foundation grant CCR18547795; the American Institute for Cancer Research grant 208537; National Cancer Institute grants R01CA253329 and R21CA249349; ASTRO-BCRF Career Development Award 637969; Breakthrough Awards from the Department of Defense Breast Cancer Research Program W81XWH-20-1-0014 and BC170905; IRACDA PRIME K12 fellowship 1K12-GM102773; and National Cancer Center’s Comprehensive Cancer Support Grant award number P30CA012197.

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